December 4, 2020
United Kingdom Approves Use of Pfizer/BioNTech Vaccine
“I have no doubt that we’re going to see a climbing death toll … and that’s a horrific and tragic place to be. It’s going to be a very dark couple of weeks.”Josh Michaud, associate director of global health policy at the Kaiser Family Foundation
“The next few months may not be just the toughest moment of the coronavirus pandemic, but perhaps the most difficult time in the nation’s public health history. Yet, it’s not a fait accompli. We’re not defenseless. The truth is that mitigation works. But it’s not going to work if only half of us do what we need to do. Probably not even if three-quarters do.”Dr. Robert Redfield, head of the Centers for Disease Control and Prevention
“It’s time to cancel everything.”LA Mayor Eric Garcetti, announcing new restrictions
Navigational Tips: Except for the stories listed under Linked Stories, all of the stories listed below are included in this update. And to the extent available, we have embedded links in the title of the stories to the extent available so that you can quickly jump to the original story on the internet if you want by clicking on the title. If you reading the Word document, you can jump to a section by holding down the control key+clicking on the title of the section.]Highlighted stories includes information we found interesting. An (!) indicates a story that includes new, promising/breakthrough or unexpected/surprising information. A (*) indicates information that may be useful in connection with your plans and preparations regarding the coronavirus and C19. And © indicates that a story contains information that may contradict or be inconsistent with other information.
- Cases & Tests
- Top 5 States in Cases, Deaths, Hospitalizations & Positivity
- U.S. Deaths Hit a Daily Record as Newly Reported Cases Surge
- Bad as things are, the worst is yet to come
- Immune system responds strongly in asymptomatic C19 (!)
- Differences in immunity and blood vessels likely protect children from severe C19
- New coronavirus crosses membranes between throat and brain
- Social Distancing Isn’t Enough Indoors (*)
- Air quality influences the pandemic (!)
- C19 research should focus more on the role of mucous membranes
- ‘Absolutely remarkable’: No one who got Moderna’s vaccine in trial developed severe C19
- New Vaccine Candidate Protects Against Coronavirus and Yellow Fever
- Spit in a Tube and Mail It In: A New Frontier in Coronavirus Testing
- CDC to shorten C19 quarantine to 10 days, 7 with test
- First Covid vaccines to be offered to health workers, nursing homes
- Oral drug blocks coronavirus transmission (!)
- Metformin reduces C19 death risks in women
- For Covid Long-Haulers, a Little-Known Diagnosis Offers Possible Treatments—and New Challenges
- Vaccination against tuberculosis can reduce the spread of C19 and ease its course
- Medicine-carriers made from human cells can cure lung infections
- Kidney disease leading risk factor for being hospitalized with C19
- Could COVID delirium bring on dementia?
- “We can only speculate”: The miraculous Swiss C19 turnaround
- C19 Likely Began in U.S. in Mid-December 2019
- How a Bidding War for C19 Nurses Hurts the Pandemic Response
- University reopenings tied to some C19 spikes
- School closures have cost an estimated 5.5 million years of life lost
- New Dynamic Global COVID Surveillance System Predicts Direction, Speed and Acceleration of Virus (!)
L. Linked Stories
- Warning: Bleach-Alternative C19 Surface Disinfectants May Pollute Indoor Air (*)
- There Many Different C19 Tests – Which One to Choose? (*)
- Pets, Touch and C19: Why Our Cats, Dogs and Other Furry Friends Are Lifesavers (*)
- What makes certain groups more vulnerable to C19?
- Comparison of coronavirus antibody tests reveals that claims were too optimistic (*)
- Daily data from COVID app predicts local incidence and prevalence of virus
- Less C19 transmission seen in countries with more intense testing
- No country ‘immune’ to C19 economic shock, but Asian nations will bounce back faster
- Study sheds light on immune mechanism that triggers cytokine storm typical of C19
- Alcohol-free hand sanitizer just as effective against COVID as alcohol-based versions (*)
- C19 may deepen depression, anxiety, and PTSD among pregnant and postpartum women
- There absolutely will be a black market’: How the rich and privileged can skip the line for C19 vaccines
- ‘It will change everything’: DeepMind’s AI makes gigantic leap in solving protein structures
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A. Pandemic Headlines
(In no particular order)
- Pfizer slashes COVID-19 vaccine rollout target in half after supply chain issues
- European officials say UK rushed approval of Pfizer COVID-19 vaccine
- US hopes to vaccinate 20,000,000 this year, 100,000,000 by end of February
- Most of the vulnerable population, 100,000,000 people, could be immunized by February, COVID-19 vaccine czar says
- US official says every American who wants a COVID-19 vaccine will have one by June
- Moderna to begin testing COVID-19 vaccine in children
- WHO Solidary Trial: remdesivir, hydroxychloroquine, lopinavir, and interferon had little or no effect on hospitalized patients with Covid-19
- “This Gives Some Hope” – Japanese Study Finds 98% Of COVID Patients Still Have Antibodies 6 Months Later
- US sets new single-day record for COVID-19 deaths
- US sets new record for COVID-19 cases, hospitalizations
- Stay home for the holidays or get tested twice, CDC urges
- Health officials fear ‘horrific’ COVID-19 surge is about to get worse
- CDC director warns the next few months could be ‘the most difficult in the public health history of this nation’
- CDC director warns 450,000 deaths by February
- Biden picks leaders for his COVID-19 response
- Biden speaks with Fauci, asks him to be ‘chief medical adviser’
- As the U.K. claims bragging rights for the best vaccine regulators (yes, really), U.S. officials beg to differ
- NYC’s COVID rates are surging as second wave rises, Mayor de Blasio warns
- NYC’s COVID-19 infection rate nears 5% — highest since May
- California to shut-down hardest-hit regions amid COVID-19 spike
- California will impose stay-at-home orders in areas where intensive care units are close to capacity
- Minnesota has caught up with North Dakota and South Dakota on the list of the hardest-hit states
- In Puerto Rico, Gov. Wanda Vázquez ordered a new partial lockdown that will force most businesses to close on Sundays and ban weekend alcohol sales until Jan. 7
- LA Mayor Bans Unnecessary Walking As Part of New COVID-19 Restrictions
- LA County Mayor Says Not Wearing A Mask Is “Act Of Domestic Terrorism”
- Ohio adds Ohio to its COVID-19 travel advisory map
- Arizona sees record deaths
- Italy sees record deaths
- Indonesia reports new record cases
- India reports 35,500 new cases
- Tokyo sees 533 new infections
- Germany extended its lockdown, which includes the closure of bars and restaurants, to Jan. 10, three weeks after its restrictions were scheduled to expire
- Greece is also extending its national lockdown, which was set to end on Dec. 7, by one week, a decision the government said was unavoidable with new daily infections steadily rising and a sharp spike in deaths
- Austria will loosen its lockdown, but bars and restaurants will remain closed until at least Jan. 7 and quarantines will extend to 10 days for arriving travelers
- Moscow will open 70 vaccination centers with teachers, doctors and social workers the first in line to receive the Russian-made Sputnik V vaccine
- Virginia County Votes To Reject Gov. Northam’s Coronavirus Restrictions
- NY expects 170,000 doses of Pfizer’s COVID-19 vaccine by mid-December
- Obama, Bush and Clinton will take coronavirus vaccine and might film it to build confidence
- Nursing homes are still getting pummeled by the pandemic
- Lubbock, Texas, is out of hospital beds
- As hospitals fill with virus patients, travel nurses who race to virus hot spots have become more urgently needed than ever
- Ambulance companies at a breaking point after receiving little Covid aid
- Civilian NYPD employees to start working remotely as COVID-19 cases spike
- Researcher Finds Evictions Are Associated With More Than 10,000 Deaths From COVID-19
- African malaria deaths set to dwarf covid-19 fatalities as pandemic hits control efforts, WHO warns
- Welsh Government Says People Will Get ID Cards To Prove They’ve Been Vaccinated
- Couple with COVID-19 arrested for boarding flight to Hawaii
- Owner Of NYC Bar Arrested Days After Declaring “Autonomous Zone” To Dodge Pandemic Restrictions
- Stay home this Christmas, a Canadian premier begs citizens
- Facebook said it would remove posts that contain claims about Covid-19 vaccines that have been debunked by public health experts
- Austin Mayor Flew Private to Cabo San Lucas Where He Filmed Himself Telling Citizens to ‘Stay Home’
- Scammers likely to make $3 million tricking lonely pet lovers during COVID-19
- Sundance Film Festival going mostly virtual, will also host satellite screenings
- Prince Harry: COVID-19 is what we get for messing with ‘Mother Nature’
- Airbnb is making it tougher to rent homes on New Year’s Eve
- The global economy could suffer without equitable access to vaccines, a report finds
- Transportation Capacity Tightens Further, Pricing Climbs Higher
- Masked workers face harassment spike: ‘Wish I could see your pretty lips’
- Ho, ho — Whoa! Virus keeping most Santas at a distance
- Scrap car company will let you shoot, destroy cars to let out 2020 rage
- Yule be sorry? Town hosting Christmas parade in defiance of COVID orders
B. Numbers & Trends (12/3)
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.
1. Cases & Tests
- Total Cases = 65,516,814
- New Cases (7 day average) = 591,546
- Record high number of new cases (679,194)
- 7 day average of new cases has started to increase after declining for a few days (7 day average is 2nd highest)
US Cases & Testing:
- Total Cases = 14,535,196
- New Cases (7 day average) = 176,145
- Percentage of New Global Cases = 29.8%
- Total Number of Tests = 201,769,463
- Percentage of positive tests (7 day average) = 13.3%
- Record high number of new cases (218,576)
- Record high 7 day average of new cases
- 7 day average percentage of positive tests has begun increasing again
- Total Deaths = 1,511,105
- New Deaths (7 day average) = 10,481
- Record high number of new cases
- Record high 7 day average of new deaths
- Total Deaths = 282,829
- New Deaths (7 day average) = 1,876
- Percentage of Global New Deaths (7 day average) = 17.9%
- Record high number of new deaths (2,918)
- Record high 7 day average of new deaths
- Percentage of Global New Deaths is increasing
3. Top 5 States in Cases, Deaths, Hospitalizations, ICUS Patients & Positivity (12/3)
- After trending down since 11/18, the US positivity % increased to 13.3% from 11.9% on 11/30. This may represent an early sign of a Thanksgiving spread.
- ND retains the lead at 54.0%, down from 57.3% a week ago
- Overall, 9 states reported lower positivity rates over the last seven days.
- Six states (ID, KS, SD, MO, NE, IA) 7-day positivity rates greater than 40%. (+2 since 11/26)
- Eight states (NV, WI, OR, IN, UT, AL, PA, RI) 7-day positivity rates greater than 30%. (+2 since 11/26)
- Seven states (CO, MN, AZ, NH, DE, WY, MT) had 7-day positivity rates greater than 20%. (+2 since 11/26)
- In total, 42 states have 7-day positivity rates greater than 5% (+3 since 11/26)
- Hospitalizations in the US have increased to 100,667, up 11.3% since 11/26. While hospitalizations are still increasing, the weekly percentage increase on 11/30 was 11.9%.
- 30 states have had increases of hospitalized patients of more than 10% since 11/26. (+3 since 11/30)
- 31 states have more than 1,000 hospitalized patients (+1 since 11/30)
- Ten states saw decreases in the number of hospitalized patients (KS, IA, NE, WI, IL, SD, HI, MN, ND, IN). (+1 since 11/30)
Patients in ICU
- ICU Patients in the US have increased to 19,442 up from 17,804 (+ 9.2%) since 11/26. While ICU patients have increased, the weekly percentage increase has fallen from 15.3% on 11/24
- 18 states have seen the number of ICU patients increase by more than 10% since 11/24 (+2 since 11/30)
- 31 states have more than 100 patients in ICU, (+1 states since 11/30)
- 11 states (VT, IA, KS, WI, AR, IL, MT, MN, MI, ME, ID) saw decreases in the number of ICU patients since 11/17 (-1 since 11/30)
4. U.S. Deaths Hit a Daily Record as Newly Reported Cases Surge
What to Know
- The number of U.S. deaths reported in a single day hit a record.
- Newly reported infections also surged, hitting 200,000 for the second time.
- Senate leaders said compromise on a coronavirus stimulus package was within reach.
- Pfizer said it expected to ship about half of the C19 vaccines it originally planned for this year after hitting supply chain snags.
- U.S. officials continued to diverge in their approaches to tamping down coronavirus infections, as the number of C19-related deaths reported in a day hit a record in the U.S., and new infections surpassed 200,000 for the second time in less than a week.
- Those new records came as hospitalizations rose to more than 100,000 for the first time on Wednesday, according to the Covid Tracking Project. The increased strain on hospitals has forced some doctors to ration intensive-care beds.
- California, facing an onslaught of new cases, is preparing to issue new stay-at-home orders based on hospital capacity in five state regions, Gov. Gavin Newsom said Wednesday. The orders will be issued once a region’s hospital intensive-care unit availability drops below 15%.
- California’s actions contrast with neighboring Arizona, where the 14-day average of new cases has topped highs not seen since summer, when the state emerged as a Covid hotspot.
- Gov. Doug Ducey on Wednesday rolled out plans to make it easier for restaurants to expand outdoor dining spaces and tightened some rules on gatherings of more than 50 people. But he stopped short of announcing a statewide curfew or large shifts in policy, like implementing a statewide mask mandate.
- Mr. Ducey criticized a nightly curfew approved this week by the mayor and city council of Tucson. “I don’t think it’s the right approach,” Mr. Ducey said Wednesday. “We want to do things that will allow businesses to operate safely.”
- In Idaho, Central District Health, which covers the state’s most populated areas, including Boise, is considering a new public- health order that would expand mask requirements, limit public and private gatherings to 10 people and prohibit most sporting events. The proposal is up for public review and comment on Friday.
- New York City Mayor Bill de Blasio warned that a “second wave” of the coronavirus pandemic was closing in on the city, which is nearing or above the three main benchmarks set earlier this year to warn of another surge.
- Mr. de Blasio said hospital systems and patients were faring better than in the spring when facilities were overwhelmed and tens of thousands of people died. But he repeated recent calls for people over 65 years old, who are at greatest risk of C19, to stay indoors as much as possible.
5. Bad as things are, the worst is yet to come
- Nine months after the initial outbreak, the United States, by our best indicators, has never been in a worse position in the pandemic.
- Across the country, more than 100,000 people are hospitalized with C19, a record that is nearly double the high point in the spring, when the pandemic reached its first peak. The country also recorded nearly 200,000 cases yesterday, it’s second highest daily total since the pandemic began, and today surpassed a total of 14 million infections.
- But no indicator is more consequential, or gut-wrenching, than the death rate — and yesterday 2,885 people died from C19, more than the record set in April, when the pandemic first peaked.
- Sadly, all indications point to things probably getting much worse.
- When there are so many cases in so many places, as there are now, it becomes much more difficult to bend the curve — it’s like turning around an aircraft carrier, Dr. Anthony Fauci told me recently.
- The April peak was the worst moment in the spring. Deaths dropped after lockdowns were imposed, Americans changed their behavior and the summer months arrived.
- Now, however, there’s no interruption in sight. The delayed effects of Thanksgiving travel and gatherings are likely to push the cases, hospitalizations and deaths higher. The communal rituals of support and hope that helped get the country through the first surge — like the nightly pot-banging salutes to health care workers — have disappeared. Pandemic fatigue and winter’s grim chill make the appeal of December holiday gatherings even more difficult to resist.
- Dr. Robert Redfield, the head of the Centers for Disease Control and Prevention, said on Wednesday that he thought that the next few months may not be just the toughest moment of the coronavirus pandemic, but perhaps the most difficult time in the nation’s public health history.
- But there is still time to turn things around, he said, if Americans would just take measures to slow the spread, like wearing masks.
- “It’s not a fait accompli,” he said. “We’re not defenseless. The truth is that mitigation works. But it’s not going to work if half of us do what we need to do. Probably not even if three-quarters do.”
Source: The New York Times Coronavirus Briefing
C. New Scientific Findings & Research
1. Immune system responds strongly in asymptomatic C19
- Asymptomatic people infected with C19 are mounting robust immune responses that differ from responses in those who become ill, according to a study that appears to contradict previous thinking by health experts. Researchers studied immune system T cells in 76 symptomatic C19 patients and 85 infected individuals without symptoms and reported their findings on Friday on bioRxiv ahead of peer review.
- Some of these cells – CD8+ T cells – can recognize virus-infected cells and destroy them. They also produce inflammatory proteins, or cytokines, that help to prevent the virus from making copies of itself. Others known as CD4 helper T cells help the body produce B cells, which make antibodies. Everyone in the study had similar frequencies of T cells that could recognize the virus and destroy infected cells, regardless of whether they had symptoms.
- But the T cells of asymptomatic individuals produced higher levels of cytokines important for fighting the virus, including interferon-gamma and interleukin-2. “What we still need to understand is whether those T cells can persist over time and offer long-term immunity,” said coauthor Antonio Bertoletti of Duke-NUS Medical School, Singapore.
2. Differences in immunity and blood vessels likely protect children from severe C19
- Differences in the immune systems and better blood vessel health were among the factors protecting children from severe C19, according to a new review.
- A huge body of global C19 literature was reviewed by experts at the Murdoch Children’s Research Institute (MCRI), the University of Melbourne and the University of Fribourg and published in the Archives of Disease in Childhood to unravel the reasons for age-related differences in C19 severity and symptoms.
- MCRI and University of Melbourne Professor Nigel Curtis said that while a number of hypotheses provided potential explanations as to why adults were at higher risk and children protected from severe disease and death from C19, most do not explain why C19 severity rises steeply after the age of 60-70 years.
- Professor Curtis said in stark contrast to other respiratory viruses, severe disease and death due to C19 was relatively rare in children.
- “Most children with C19 have no or only mild symptoms, most commonly fever, cough, sore throat and changes in sense of smell or taste,” he said. “Even children with the usual risk factors for severe infections, such as immunosuppression, were not at high risk of severe C19 disease.”
- Professor Curtis said damage to the thin layer of endothelial cells lining various organs, especially the blood vessels, heart, and lymphatic vessels, increased with age and there was an association between conditions that affect these cells and severe C19.
- “We know pre-existing blood vessel damage plays an important role in C19 severity and can lead to blood clots, causing strokes and heart attacks. C19 can infect these endothelial cells and cause blood vessel inflammation,” he said.
- “The endothelium in children has experienced far less damage compared with adults and their clotting system is also different, which makes children less prone to abnormal blood clotting.”
- Professor Curtis said diseases associated with chronic inflammation that develop with advanced age including diabetes and obesity were also linked with severe C19.
- He said more recent immunization with live vaccines, such as the MMR vaccine against measles, mumps, and rubella, that could boost the immune system might play a role in protecting children.
- Dr Petra Zimmermann from the University of Fribourg said there were also other important differences in the immune system between children and adults.
- “Children have a stronger innate immune response, which is the first-line defense against C19,” she said.
- “Another important factor is ‘trained immunity’ which primes innate immune cells after mild infections and vaccinations, leading to a type of ‘innate immune memory’.
- “Children infected with C19 often have co-infections with other viruses. Recurrent viral infections could lead to improved trained immunity, making kids more effective at clearing C19.”
- Dr Zimmermann said different levels of microbiota (bacteria and other germs) in the throat, noise, lung and stomach, also influenced susceptibility to C19.
- “The microbiota plays an important role in the regulation of immunity, inflammation and in the defense against illnesses,” she said. “Children are more likely to have viruses and bacteria, especially in the nose, where these bugs might limit the growth of C19.”
- Dr Zimmermann said the vitamin D level, with its anti-inflammatory properties, was also generally higher in children.
- “The overlap between risk factors for severe C19 and vitamin D deficiency, including obesity, chronic kidney disease and being of black or Asian origin, suggests that vitamin D supplementation may play a role in helping prevent or treat C19,” she said.
- “In many countries, vitamin D is routinely supplemented in infants younger than one year of age and in some countries even up to the age of three years.”
- Professor Curtis said understanding the underlying age-related differences in the severity of C19 would provide important insights and opportunities for prevention and treatment of SARS-CoV-2 infections.
3. New coronavirus crosses membranes between throat and brain
- The novel coronavirus uses the nose as a gateway into the brain, autopsy findings suggest. The presence of the virus in the brain and cerebrospinal fluid has been linked with neurological symptoms, but exactly how the virus enters the central nervous system has not been clear.
- During autopsies of 33 patients who died of C19, researchers examined the nasopharynx – the region where the nasal cavity connects with the back of the throat – which happens to be in close proximity to the brain. By dissecting cells and following the path of infection, they saw that the virus invades the brain by crossing through the mucous membranes that separate it from the nasopharynx.
- From there, according to a report published on Monday in Nature Neuroscience, the virus may travel along the nerve fibers that connect the nasal cavity to the part of the brain involved in the sense of smell, which would explain “some of the well-documented neurological symptoms in C19, including alterations of smell and taste perception.”
- The researchers also found virus particles in brain regions with no direct connection to the nose, which suggests there may be additional routes of viral entry into the brain.
4. Social Distancing Isn’t Enough Indoors
Understanding Dangerous Droplet Dynamics
- New fluid dynamics research reveals why social distancing alone doesn’t necessarily prevent infection indoors and how to detect C19 super-spreaders.
- Researchers who study the physics of fluids are learning why certain situations increase the risk that droplets will transmit diseases like C19.
- At the 73rd Annual Meeting of the American Physical Society’s Division of Fluid Dynamics, the scientists offered new evidence showing why it’s dangerous to meet indoors — especially if it’s cold and humid, and even if you’re more than six feet away from other people. They suggested which masks will catch the most infectious droplets. And they provided new tools for measuring super-spreaders.
- “Present epidemiological models for infectious respiratory diseases do not account for the underlying flow physics of disease transmission,” said University of Toronto engineering professor Swetaprovo Chaudhuri, one of the researchers.
- But fluids and their dynamics are critical for shaping pathogen transport, which affects infectious disease transmission, explained mathematical physicist and professor Lydia Bourouiba, Director of The Fluid Dynamics of Disease Transmission Laboratory at MIT. She gave an invited talk on the body of work she has produced over the last ten years elucidating the fluid dynamics of infectious diseases and disease transmission.
- “My work has shown that exhalations are not isolated droplets but in fact come out as a turbulent, multiphase cloud. This gas cloud is critical in enhancing the range and changing the evaporation physics of the droplets within it,” said Bourouiba. “In the context of respiratory infectious diseases, particularly now C19, this work underscores the importance of changing distancing and protection guidelines based on fluid dynamics research, particularly regarding the presence of this cloud.”
- Bourouiba presented examples from a range of infectious diseases including C19 and discussed the discovery that exhalation involves different flow regimes, in addition to rich unsteady fluid fragmentation of complex mucosalivary fluid. Her research reveals the importance of the gas phase, which can completely change the physical picture of exhalation and droplets.
- Nordic Institute for Theoretical Physics scientist Dhrubaditya Mitra and his team realized they could use the mathematical equations that govern perfume to calculate how long it would take for viral droplets to reach you indoors. It turns out: not very long at all.
- “It showed us how futile most social distancing rules are once we are indoors.” — Dhrubaditya Mitra
- Perfume worn by someone at the next table or cubicle reaches your nose thanks to turbulence in the air. Fine droplets spewed by an infected person spread in the same way. The researchers found that below a relative distance known as the integral scale, droplets move ballistically and very fast.
- Even above the integral scale, there is danger. Consider an example where the integral scale is two meters. If you were standing three meters — just under ten feet — from an infected person, their droplets would almost certainly reach you in about a minute.
- “It showed us how futile most social distancing rules are once we are indoors,” said Mitra, who conducted the research with colleague Akshay Bhatnagar at the Nordic Institute for Theoretical Physics and Akhilesh Kumar Verma and Rahul Pandit at the Indian Institute of Science.
- Besides traveling further and faster, droplets may also survive longer indoors than previously believed.
- Research in the 1930s analyzed how long respiratory droplets survive before evaporating or hitting the ground. The nearly century-old findings form the basis of our current mantra to “stay six feet away” from others.
- Physicists from the University of Twente revisited the issue. They conducted a numerical simulation indicating that droplet lifetimes can extend more than 100 times longer than 1930s standards would suggest.
- “Current social distancing rules are based on a model which by now should be outdated,” said physicist Detlef Lohse, who led the team.
- In a cold and humid space, exhaled droplets don’t evaporate as quickly. The hot moist puff produced also protects droplets and extends their lifetimes, as do collective effects.
- “Current social distancing rules are based on a model which by now should be outdated.” — Detlef Lohse
- Some droplets are more likely than others to make you sick. University of Toronto’s Chaudhuri, with researchers from the Indian Institute of Science and the University of California San Diego, investigated why, using human saliva droplet experiments and computational analyses.
- They found that some of the most infectious droplets start out at 10 to 50 microns in size. “With certain assumptions, it appears that if everyone wears a mask that can prevent ejection of all droplets above 5 microns, the pandemic curve could be flattened,” said Chaudhuri.
- Dried droplet residue also poses a serious risk: It persists much longer than droplets themselves and can infect large numbers of people if the virus remains potent.
- The team used their findings to develop a disease transmission model. “Our work connects the microscale droplet physics and its fundamental role in determining the infection spread at a macroscale,” said Chaudhuri.
- To better understand droplet dynamics in the C19 pandemic, a team from Northwestern University and the University of Illinois at Urbana-Champaign tested the capacities of a new wearable device. The thin, wireless, flexible sensor attaches like a sticker to the bottom of the neck to capture vital signals. Ongoing clinical studies are using the device with hospital patients.
- The team found that the device distinguishes between coughing, talking, laughing, and other breathing activities with its machine learning algorithms. Researchers used particle tracking velocimetry and a decibel meter to analyze droplets produced by device wearers.
- “Different types of speech can generate drastically different numbers and dynamics of droplets,” said biomedical engineering researcher Jin-Tae Kim, who led the investigation.
- The device can help shed light on why some individuals become unusually infectious — the so-called super-spreaders. “Our findings further address the critical need for continuous skin-integrated sensors to better comprehend the pandemic,” said Kim.
- Watch a video below.
5. Air quality influences the pandemic
- The correlation between the high concentration of fine particles and the severity of influenza waves is well known to epidemiologists. An interdisciplinary team from the University of Geneva (UNIGE) and the ETH Zürich spin-off Meteodat investigated possible interactions between acutely elevated levels of fine particulate matter and the virulence of the coronavirus disease. Their results, published in the journal Earth Systems and Environment, suggest that high concentrations of particles less than 2.5 micrometers in size may modulate, or even amplify, the waves of the coronavirus (SARS-CoV-2) contamination and explain in part the particular profile of the C19 pandemic. The increase in fine particles is generally favored by air temperature inversions, characterized by fog situations, or by Saharan dust intrusions. The study provides preventive measures related to air pollution to limit future outbreaks of morbidity and mortality due to the coronavirus.
- Epidemiologists widely agree that there is a correlation between acute and locally elevated concentrations of fine particles and the severity of influenza waves. “We have investigated whether such a link also exists with the virulence of C19 disease,” says Mario Rohrer, researcher at the Institute for Environmental Sciences of the Faculty of Sciences of UNIGE and director of Meteodat.
A surprising time lag
- C19 studies conducted in Italy and France suggest that SARS-CoV-2 was already present in Europe at the end of 2019, while the sharp increase in morbidity and mortality was only recorded in spring 2020 in Paris and London. “This time lag is surprising, but also suggests that something else than just the mere interaction of people may promote the transmission of the virus, and particularly the severity of the infection,” says Mario Rohrer. His research team has been able to show that these increases in cases followed phases where the levels of fine particles in the air were higher.
- The team made similar observations in the Swiss canton of Ticino, where fine-particle pollution increased sharply during a period of shallow fog on the Magadino plain and the Sotto Ceneri, observed at the end of February 2020. “Shortly afterwards, an explosive increase in hospital admissions due to C19 was recorded in Ticino. The fact that a large carnival event with some 150,000 visitors took place at the same time probably had an additional impact on the spread of the virus,” says Mario Rohrer.
- The information is important for Switzerland because the increase in fine particle concentrations is particularly frequent during thermal inversions, i.e. when fog forms on the Swiss Plateau, thus limiting the exchange of air masses. In these situations, emissions accumulate in the layer of air underneath the fog. Switzerland is also frequently swept by dust from Saharan sandstorms, also pointed out in this study.
- The Swiss research team shows that acute concentrations of fine particles, especially those smaller than 2.5 micrometers, cause inflammation of the respiratory, pulmonary and cardiovascular tracts and thicken the blood. “In combination with a viral infection, these inflammatory factors can lead to a serious progression of the disease. Inflammation also promotes the attachment of the virus to cells,” he says. In addition, the coronavirus may also be transported by the fine particles. “This has already been demonstrated for influenza and an Italian study found coronavirus RNA on fine particles. All this remains to be demonstrated, of course, but it is a likely possibility,” adds Rohrer.
A multifactorial pandemic
- Nonetheless, the researchers also emphasize that, although particulate matter pollution can influence the virulence of the virus and possible severe disease progression, physiological, social or economic factors will clearly also influence the further course of the pandemic. Mario Rohrer concludes that the findings of this study offer the possibility of taking preventive measures in the event of future increases in fine particulate matter concentrations, thus limiting a new flare-up of C19 morbidity and mortality.
6. C19 research should focus more on the role of mucous membranes
- Anyone who has undergone a nasal swab or saliva test for C19 knows that the virus is most easily detected in the nose and mouth. That’s why, University at Buffalo researchers argue in a new paper, more C19 studies should be devoted to how immunity emerges to the coronavirus (SARS-CoV-2) in the mucous membranes of the nose and mouth.
- The paper was published Nov. 30 in Frontiers in Immunology.
- Noting that the mucosal immune system is the immune system’s largest component, the researchers expressed concern that it hasn’t been a focus of much of the research on C19 to date.
- “We think it is a serious omission to ignore the mucosal immune response to SARS-CoV-2, given its initial sites of infection,” said Michael W. Russell, PhD, emeritus professor, Department of Microbiology and Immunology in the Jacobs School of Medicine and Biomedical Sciences at UB, and senior author on the paper. “Clearly the response of the systemic immunoglobulin G antibody [the most abundant circulating antibody] is important — we do not deny that — but on its own it is insufficient.”
- Russell noted that naturally, the initial focus of research on the disease was on cases of severe disease when the virus descends into the lower respiratory tract, especially the lungs, where the cellular immune responses exacerbate the inflammation rather than fight the infection.
- But since the upper respiratory tract, including the nose, tonsils and adenoids are the initial point of infection for the SARS-CoV-2 virus, the immune responses that are triggered there are of special interest.
- In addition, the high rate of asymptomatic transmission of C19, which the Centers for Disease Control and Prevention recently estimated at more than 50%, is another reason why mucosal immunity is so important, according to the authors.
- “Given that many infected people remain asymptomatic, and that a large number of those who develop symptoms suffer only mild to moderate disease, this suggests that something, somewhere, does a fairly good job of controlling the virus,” said Russell.
- “Could it be that this is due to early mucosal immune responses that succeed in containing and eliminating the infection before it becomes serious?” he asked. “We will not know unless these questions are addressed.”
- The paper recommends that studies are needed to determine the nature of mucosal secretory immunoglobulin A (SIgA) antibody responses over the course of infection, including asymptomatic or pre-symptomatic infection, and mild and moderate cases of C19 disease. In addition, the authors point out that the mucosal immune responses may vary depending on different age groups and populations.
- A focus on mucosal immunity might also make it possible to develop a type of vaccine, such as a nasal vaccine, that could be easier to store, transport and administer. Several such vaccines are now under development for C19 but how far along they are is unknown.
- Russell added that these vaccines might not have special temperature requirements and might be more palatable for large swaths of the population, especially children, because they would not require an injection.
Potential advantages of a mucosal vaccine
- “The potential advantage of a mucosal vaccine – especially one that is intranasal – is that it should induce immune responses, including SIgA antibodies, in the mucosal tracts, in this case especially the upper respiratory tract, where the coronavirus makes first contact,” explained Russell, adding that injected vaccines usually do not do this.
- Among the areas of study that the authors suggest would be constructive are molecular studies on IgA antibodies and their relationship to the disease stage of C19, and determining the characteristics of cells that secrete IgA antibodies and other mucosal immune cells induced by the infection or by vaccination.
- “As mucosal immunologists with several decades of experience behind us, we have been perturbed at the lack of attention to this, and we hope to draw attention to this glaring omission,” said Russell. “After all, the mucosal immune system is by far the largest component of the entire immune system, and it has evolved to protect the mucosal surfaces where the great majority of infections arise.”
D. Vaccines & Testing
1. ‘Absolutely remarkable’: No one who got Moderna’s vaccine in trial developed severe C19
- Continuing the spate of stunning news about C19 vaccines, the biotech company Moderna announced the final results of the 30,000-person efficacy trial for its candidate in a press release today: Only 11 people who received two doses of the vaccine developed C19 symptoms after being infected with the pandemic coronavirus, versus 185 symptomatic cases in a placebo group. That is an efficacy of 94.1%, the company says, far above what many vaccine scientists were expecting just a few weeks ago.
- More impressive still, Moderna’s candidate had 100% efficacy against severe disease. There were zero such C19 cases among those vaccinated, but 30 in the placebo group. The company today plans to file a request for emergency use authorization (EUA) for its vaccine with the U.S. Food and Drug Administration (FDA), and is also seeking a similar green light from the European Medicines Agency.
- The data released today bolster an interim report from the company two weeks ago that only analyzed 95 total cases but produced similarly impressive efficacy. “I would still like to see all of the actual data, but what we’ve seen so far is absolutely remarkable,” says Paul Offit, a vaccine researcher at the Children’s Hospital of Philadelphia who is a member of an independent committee of vaccine experts that advises FDA.
2. New Vaccine Candidate Protects Against Coronavirus and Yellow Fever
- Virologists at the Rega Institute at KU Leuven (Belgium) have developed a vaccine candidate against Covid-19 based on the yellow fever vaccine, which as a result also works against yellow fever. Results published today in Nature show that the vaccine protects hamsters from infection with the coronavirus (SARS-CoV-2) after a single dose. The vaccine is also effective in monkeys. The team is currently preparing for clinical trials.
- To engineer their vaccine, tentatively named RegaVax, the team led by Professor Johan Neyts and Kai Dallmeier inserted the genetic code of the SARS-CoV-2 spikes into the genetic code of the yellow fever vaccine. The researchers tested the vaccine in healthy hamsters and monkeys. Another group of the animals received a placebo.
- The researchers first vaccinated the hamsters and then dripped the virus into their noses. Ten days after a single vaccine dose, most of the hamsters were protected against the virus. Three weeks after vaccination, all hamsters were protected. “They also didn’t develop any lung infections. The lungs of the hamsters in the control groups, by contrast, showed clear signs of infection and disease,” Neyts explains.
- The team also tested the vaccine in monkeys. “In some of the monkeys, we observed neutralizing antibodies already seven days after vaccination. After fourteen days, high titers of neutralizing antibodies were measured in all animals. This is very fast. Moreover, in the vaccinated animals, the virus was completely or nearly completely gone from their throats.”
- “Ours is the only vaccine currently in development against C19 that also protects against yellow fever,” explains professor Neyts. Previously, the Rega team used the yellow fever vaccine as the foundation for vaccine candidates against Zika, Ebola, and rabies. “The effectiveness and safety of the yellow fever vaccine, which has been in use for 80 years, is well-established. More than 500 million people have already received this vaccine. One dose offers fast protection against yellow fever that in nearly all cases lasts for life.”
- “A vaccine that works against C19 and yellow fever could offer an important contribution to the WHO’s campaign to eradicate yellow fever by 2026,” Neyts continues. “Especially now that we know there are mosquito species present in Asia that can transmit the yellow fever virus.”
- RegaVax works after one dose, unlike many of the front-runners in the race today, which require a repeat vaccination after one month. “This has important logistical implications, in particular for countries with a less advanced medical system,” explains professor Neyts. “Additionally, we expect that the vaccine will offer long-lasting immunity to C19. It could therefore be an ideal candidate for repeat vaccinations when immunity decreases in people who have received one of the first-generation vaccines.”
- Finally, the vaccine can be stored at 2-8 °C, while some vaccines require a cold chain with temperatures down to -70 °C. That’s already challenging in the Western world, but it may be nearly impossible to vaccinate large populations in remote tropical and subtropical regions,” Neyts explains.
- “An inexpensive, single-dose vaccine that rapidly protects against infection, that can be stored and transported at fridge temperature, and that may, like the yellow fever vaccine on which it is based, result in long-lasting immunity, provides an important and much-needed diversification of the C19 vaccine landscape,” Neyts concludes.
- His team is now preparing for clinical trials next year and has joined forces with a specialized and accredited company that will produce the vaccine candidate for testing in humans.
- RegaVax is a vector vaccine: it uses the genetic code of the yellow fever vaccine virus as a carrier (or vector) for the genetic code of the coronavirus spikes. “When working with a related virus, such as the Zika virus, pieces of the genetic code of the yellow fever vaccine virus are swapped with a similar piece of the code of the targeted virus. Using this strategy the team recently developed a Zika vaccine candidate. However, since SARS-CoV-2 is unrelated to yellow fever, a new technology had to be developed to insert an entirely unrelated genetic sequence in the yellow fever vaccine backbone. This concerns an important innovation in the vaccine field.”
- “Mind you: vaccines are not a solution for people who are already ill. That is why we are also developing a cure to help C19 patients,” Neyts concludes. “We recently published on the protective activity of the Japanese flu drug favipiravir in hamsters. We have identified some other existing medicines or combinations thereof that inhibit the virus. We are now first exploring their effect in infected hamsters. At the same time, we aim to develop new and powerful virus inhibitors against SARS-CoV-2. For this purpose, we have already tested more than 1.6 million molecules in our fully automated high biosafety laboratory. We’re looking for a needle in a haystack.”
3. Spit in a Tube and Mail It In: A New Frontier in Coronavirus Testing
- The post-Thanksgiving rush for coronavirus testing is on: Pharmacies in the Southern California suburbs are advising customers lucky enough to score appointments that it could be four days before they receive results. In Chelsea, Mass., a line of people who hoped for testing, pelted by rain and wind, strung along an entire block early this week. In Atlanta, people have idled in cars, sometimes for hours, to get swabbed at drive-throughs.
- Testing has long been one of the keys to controlling the spread of a virus that with the onset of winter is entering its most dangerous phase. Yet even as cases per capita have rocketed, securing a test has become enough of an ordeal that many people have been dissuaded from even trying.
- That has begun to change in recent weeks as a handful of communities across the country have rolled out the first do-it-yourself home saliva tests, which require users to simply dribble into a test tube, seal it and send it to a lab. As the tests become widespread, they could provide a less-uncomfortable alternative to nasal swabs and enable more people to safely return to work and school in the months before a vaccine is widely available.
- In California, Orange County, home to Disneyland and Surf City, last week kicked off an ambitious effort to distribute 500,000 home-use saliva test kits to its 3.4 million residents by the end of December. Its initial push has focused on Anaheim and Santa Ana, the two most populous cities where the pandemic has taken an outsize toll on the Latino and immigrant populations.
- Among those who stopped by to collect kits outside the Family Health Matters clinic was Sandra Reyes-Aceves, 48, who lives with her two teenage children and aging parents in Anaheim.
- “This is the best thing for my parents’ safety. I don’t have to make them leave the house to get tested,” Ms. Reyes-Aceves said. Though no one in her family has symptoms, she said, she worries that she or the children could have the virus and not know it.
- Public health officials have long hoped that combining the ease of saliva sampling with at-home collection would open important new windows into the spread of the virus and help persuade those who did not know they were infected to stay home and limit further transmission.
- “The big issue is, how do you get more people to get tested,” said Anne Rimoin, a professor of epidemiology at the U.C.L.A. Fielding School of Public Health. “Everyone has seen lines looping around stadiums and urgent cares.”
- A test people can do at home and mail in “really helps,” she said. “It isn’t going to end the pandemic, but it is certainly a major step toward making testing more accessible and widespread.”
- Minnesota, now with one of the highest rates of new cases in the country, became the first state, in early November, to offer at-home saliva testing for all residents, whether they have coronavirus symptoms or not.
- Once a testing kit is ordered, it is typically shipped within 24 hours. During sample collection, users are supervised via Zoom by a health worker at Vault Health, the company contracted by Minnesota’s Health Department to manage the tests. Results are available in 24 to 48 hours.
- “With community spread at such high levels we’ve focused on removing barriers to make testing as easy and accessible as possible,” said Dan Huff, the department’s assistant commissioner for health protection.
- Thus far, 261,000 kits manufactured by Infinity BiologiX, the first home-saliva test to secure emergency use authorization from the federal Food and Drug Administration, have been distributed statewide.
- The decision to make home saliva tests available came as infection rates in Minnesota climbed to new highs. State health officials said it was too early to ascertain whether the availability of new testing was helping to contain the virus. In fact, for the time being, the tests are likely to lead to higher case numbers.
- Kristine Grover of Blackduck, Minn., said she decided to order the home test after her 12-year-old son, Keaton, came down with a fever, cough and runny nose.
- “We knew he would tolerate the saliva test better than the nasal swab,” she said. “I ordered the test on a Monday, he performed the test on Tuesday and we received the negative results on Thursday morning.”
- A well-designed saliva test can be as accurate as a nasal swab test, scientists say. Researchers have found significant levels of the coronavirus in oral secretions. Like nasal swab tests, saliva tests are based on P.C.R. technology, which amplifies small amounts of viral material for analysis.
- Sports leagues, schools and colleges were among the early adopters of saliva tests, and newly developed tests have been hitting the market after winning F.D.A. approval. Whether they could supplant nasal swab tests depends, in part, on how quickly labs can ramp up production.
- In St. Louis, the medical school of Washington University began offering a saliva test to some local teachers this week. In Greenwich, Conn., the Greenwich Academy, an all-girls private school, credits the regular use of spit tests for allowing it to stay open.
- As home test kits become more widely available, their success in mitigating the spread of the coronavirus could hinge on how often they are used. Communities offering the test generally cover the cost, if a person’s health insurance does not.
- “What is necessary is for people to test frequently,” said Jerry Cangelosi, an infectious-diseases expert at the University of Washington in Seattle. “Home testing is effective if it can be done repeatedly, such as weekly, not once a year.”
- Several counties in New Jersey also have introduced at-home saliva tests, although Burlington County suspended its home testing program after many people took kits and failed to use them. Of the more than 2,400 saliva kits requested by residents and paid for by the county since October, only 900 have been mailed into the lab.
- “Unfortunately, numerous people have requested the test kits but failed to return them with collected samples for testing, essentially keeping the kits until they decide they need them,” Herb Conaway, the county’s health director, said in a statement. “This is not how the program was intended to work.”
- In California, where a new, ominous wave of the pandemic has led to a record surge in cases, widespread testing could be crucial.
- In Orange County, the rate of new coronavirus cases has tripled over the past two weeks. While upscale coastal cities, like Newport Beach, have had relatively few cases, inland cities, like Santa Ana and Anaheim, account for a disproportionately high share of infections, hospitalizations and deaths, and the initial at-home tests are being targeted there.
- “The inability of some residents, who lack means, to work remotely or quarantine appropriately has led to a disparity in infection rates between communities,” said Andrew Do, vice chairman of the county’s board of supervisors.
- “Our challenge will be to get the message out: This is how you protect loved ones, and we’ll be able to go back to businesses and interacting with each other.”
- Unlike Orange County’s nose-swab testing program, which has targeted people with coronavirus symptoms, the in-home saliva effort is intended to widen testing to include people who might not be suffering from any symptoms.
- In the initial phase, the county has partnered with five community clinics to distribute 11,000 testing kits. The test was developed by Ambry Genetics, a local company with expertise in genetic diseases that has converted part of its lab to produce the tests.
- “Our test is literally, you spit up to a point in the tube, seal the cap and mail it in,” said Aaron Elliott, the company’s chief executive, who compared it to consumer genetics tests like those from AncestryDNA. “It’s much easier than tickling your brain with a nasal swab.”
- The county plans to open the saliva home-testing program to the entire county as Ambry Genetics ramps up production. “We’re hoping this will be a game-changer in a lot of ways,” said Doug Chaffee, a county supervisor who represents a part of Anaheim that is heavily Hispanic.
- Outside the Family Health Matters clinic, Lisa Ramos, a quality-practice specialist, sat behind a table stacked with blue-and-white boxes. Each kit contained a collection tube with a unique code, a biohazard bag in which to place the sealed tube and a prepaid FedEx envelope.
- Ms. Ramos explained in Spanish how to properly collect and return the specimens. Without asking people their names or taking any information, she instructed them to register the test online. Results are delivered by email, and those who test positive are contacted by a health care provider.
- The people who stopped by to pick up kits all said that they either lived in multigenerational homes or shared accommodation with nonrelatives and expressed concern that infection could easily spread among them.
- “This is amazing,” said Agustina Esteves, an Argentine college student who works part-time at an auto-repair shop, as she picked up three kits, for herself and two housemates. “I’m going to take the test as soon as I get home.”
- Maria Romero, 65, said she was aware the coronavirus was coursing through the Latino community, even if it had spared her household, at least as far as everyone knew.
- So she heeded the Health Department’s call to pick up a test kit for herself and four relatives with whom she lives.
- “We feel fine,” she said, “but we still could have the virus and be passing it to other people.”
4. CDC to shorten C19 quarantine to 10 days, 7 with test
- The CDC is set to shorten the recommended length of quarantine after exposure to someone who is positive for C19, as the virus rages across the nation.
- According to a senior administration official, the new guidelines, which are set to be released as soon as Tuesday evening, will allow people who have come in contact to someone infected with the virus to resume normal activity after 10 days, or 7 days if they receive a negative test result. That’s down from the 14-day period recommended since the onset of the pandemic.
- The official, who spoke on the condition of anonymity to preview the announcement, said the policy change has been discussed for some time, as scientists have studied the incubation period for the virus. The policy would hasten the return to normal activities by those deemed to be “close contacts” of those infected with the virus, which has infected more than 13.5 million Americans and killed at least 270,000.
- While the CDC had said the incubation period for the virus was thought to extend to 14 days, most individuals became infectious and developed symptoms between 4 and 5 days after exposure.
- It’s not the first time that the CDC has adjusted its guidance for the novel coronavirus as it adjusted to new research. In July the agency shortened, from 14 days to 10, its advice on how long a person should stay in isolation after they first experience COVID symptoms — provided they’re no longer sick.
- The new guidance was presented Tuesday at a White House coronavirus task force meeting for final approval.
5. First Covid vaccines to be offered to health workers, nursing homes
- Health care personnel and residents of long-term care facilities will be the first groups to be offered the C19 vaccine, according to a new proposal from an independent advisory committee within the Centers for Disease Control and Prevention.
- “We have spent eight months discussing and evaluating the data,” Dr. José Romero, ACIP chair, said following the vote. “We are using the principles of maximizing benefits and minimizing harms, promoting justice and mitigating health inequities.”
- The first phase of the vaccine rollout will be known as Phase 1a and is set to begin as soon as a vaccine receives authorization from the Food and Drug Administration, which is currently reviewing data on two vaccines, made by Pfizer and Moderna. The FDA’s advisory committee will meet on Dec. 10 to consider an emergency use authorization for the Pfizer vaccine.
- Current estimates project that no more than 20 million doses of each vaccine will be available by the end of the year. And each product requires two doses.
- As a result, the shots will be rationed in the early stages. Experts say the vaccine will probably not become widely available in the U.S. until the spring.
- The two groups in Phase 1a together represent around 24 million Americans — 21 million health care workers and 3 million residents of long-term care facilities. Staff working at long-term care facilities are considered among the health care workers.
- As the meeting got underway, panel member Dr. Beth Bell of the University of Washington noted that on average, one person is dying of C19 per minute in the U.S. right now, “so I guess we are acting none too soon.”
- During the discussion period, panel members asked about how the vaccine doses would be prioritized within the groups in Phase 1a. For example, health care workers with direct patient contact would be among the first to be offered the vaccine, as well as individuals working in long-term care facilities.
- Other questions addressed vaccine safety and adverse events monitoring after people received the vaccine.
- “We’re going to hold ourselves to an exceedingly high standard for safety monitoring after a vaccine is authorized and when it’s rolled out more broadly,” said Dr. Nancy Messioner, the head of the National Center for Immunization and Respiratory Diseases at the CDC.
- Safety monitoring will include several components, including the long-running Vaccine Adverse Event Reporting System, managed by both the CDC and FDA, and a new approach called V-SAFE, which monitors early recipients of the C19 vaccine with text messages and online surveys.
- “Long journeys begin with first steps,” he said. “And this was a firm, clear first step that health care workers and residents of long-term care facilities should be the first in the line to get the vaccine.”
- Schaffner acknowledged the concern about giving the vaccine to nursing home residents. “Will the vaccine be as effective in that group? We’ll just have to find out.”
- “There’s no right decision here, there’s no wrong decision here,” he added.
- The advisory panel will meet again in several weeks to decide who should be next in line.
- Among the possibilities: teachers, police officers, firefighters and workers in other essential fields such as food production and transportation; the elderly; and people with underlying medical conditions.
E. Improved & Potential Treatments
1. Oral drug blocks SARS-CoV-2 transmission, Georgia State biomedical sciences researchers find
- Treatment of coronavirus (SARS-CoV-2) infection with a new antiviral drug, MK-4482/EIDD-2801 or Molnupiravir, completely suppresses virus transmission within 24 hours, researchers in the Institute for Biomedical Sciences at Georgia State University have discovered.
- The group led by Dr. Richard Plemper, Distinguished University Professor at Georgia State, originally discovered that the drug is potent against influenza viruses.
- “This is the first demonstration of an orally available drug to rapidly block SARS-CoV-2 transmission,” said Plemper. “MK-4482/EIDD-2801 could be game-changing.”
- Interrupting widespread community transmission of SARS-CoV-2 until mass vaccination is available is paramount to managing C19 and mitigating the catastrophic consequences of the pandemic.
- Because the drug can be taken by mouth, treatment can be started early for a potentially three-fold benefit: inhibit patients’ progress to severe disease, shorten the infectious phase to ease the emotional and socioeconomic toll of prolonged patient isolation and rapidly silence local outbreaks.
- “We noted early on that MK-4482/EIDD-2801 has broad-spectrum activity against respiratory RNA viruses and that treating infected animals by mouth with the drug lowers the amount of shed viral particles by several orders of magnitude, dramatically reducing transmission,” said Plemper. “These properties made MK-4482/EIDD/2801 a powerful candidate for pharmacologic control of C19.”
- In the study published in Nature Microbiology, Plemper’s team repurposed MK-4482/EIDD-2801 against SARS-CoV-2 and used a ferret model to test the effect of the drug on halting virus spread.
- “We believe ferrets are a relevant transmission model because they readily spread SARS-CoV-2, but mostly do not develop severe disease, which closely resembles SARS-CoV-2 spread in young adults,” said Dr. Robert Cox, a postdoctoral fellow in the Plemper group and a co-lead author of the study.
- The researchers infected ferrets with SARS-CoV-2 and initiated treatment with MK-4482/EIDD-2801 when the animals started to shed virus from the nose.
- “When we co-housed those infected and then treated source animals with untreated contact ferrets in the same cage, none of the contacts became infected,” said Josef Wolf, a doctoral student in the Plemper lab and co-lead author of the study. By comparison, all contacts of source ferrets that had received placebo became infected.
- If these ferret-based data translate to humans, C19 patients treated with the drug could become non-infectious within 24 hours after the beginning of treatment.
- MK-4482/EIDD-2801 is in advanced phase II/III clinical trials against SARS-CoV-2 infection.
2. Metformin reduces C19 death risks in women
- University of Minnesota Medical School and UnitedHealth Group (NYSE: UNH) researchers found that metformin was associated with significantly reduced C19 death risks in women in one of the world’s largest observational studies of C19 patients.
- Metformin is an established, generic medication for managing blood sugar levels in patients with type 2 diabetes. It also reduces inflammation proteins like TNF-alpha that appear to make C19 worse.
- The study, published in The Lancet Healthy Longevity, is a retrospective cohort analysis based on de-identified patient data from UnitedHealth Group. The team analyzed about 6,000 individuals with type 2 diabetes or obesity who were hospitalized with C19 and assessed whether or not metformin use was associated with decreased mortality. They found an association that women with diabetes or obesity, who were hospitalized for C19 disease and who had filled a 90-day metformin prescription before hospitalization, had a 21% to 24% reduced likelihood of mortality compared to similar women not taking the medication. There was no significant reduction in mortality among men.
- “Observational studies like this cannot be conclusive, but contribute to growing bodies of evidence. Seeing a bigger association with protection in women over men may point towards inflammation reduction as a key way that metformin reduces risk from C19. However, more research is needed,” said principal investigator Carolyn Bramante, MD, MPH, who is an assistant professor in the Department of Medicine at the University of Minnesota Medical School. “A large database covering different geographic areas is rarely available. We were fortunate to have the opportunity to do this research alongside UnitedHealth Group.”
- “While effective therapies to mitigate the harm of the coronavirus (SARS-CoV-2) are being developed, it is important that we also look to, and evaluate commonly used medications with good safety profiles for their potential to combat the virus,” said Deneen Vojta, MD, executive vice president, Enterprise Research and Development, UnitedHealth Group.
- The results provide new directions for research against C19. In collaboration with Christopher Tignanelli, MD, assistant professor in the Department of Surgery at the University of Minnesota Medical School, Bramante submitted an investigational new drug application to the Food and Drug Administration for use of metformin for C19 treatment and prevention. The FDA approved this application. Bramante and Tignanelli received a donation from the Parsemus Foundation to conduct a multi-site prospective, randomized pilot study in collaboration with the Executive Director of Clinical Research for UnitedHealth Group R&D, Ken Cohen, MD. This pilot trial will begin enrolling the week of Dec. 8 and will lead into a larger trial that is fully powered for important clinical outcomes if additional funding becomes available. These collaborators are still seeking this funding.
3. For Covid Long-Haulers, a Little-Known Diagnosis Offers Possible Treatments—and New Challenges
- Some patients with long-term Covid symptoms are getting more potential treatment options as doctors diagnose them with a little-known syndrome called POTS.
- It’s a disorder of the autonomic nervous system that can have a variety of causes, and it existed before Covid. One common trigger is an infection, such as a virus. Now some doctors believe that the coronavirus is triggering the disorder in some people, providing an explanation for debilitating symptoms including dramatically elevated heart rates from small movements, dizziness and extreme fatigue after even minor physical activity.
- The good news, experts say, is there are protocols and treatments for POTS, which stands for postural orthostatic tachycardia syndrome. They include a guided, very gradual return to physical activity; compression stockings or abdominal compression to prevent blood pooling in the lower half of the body; increased salt and fluid intake if blood pressure is low; and sometimes medications to regulate blood pressure, heart rate and blood volume.
- But the diagnosis also brings new challenges: Even gentle attempts to resume physical activity are proving especially arduous for many post-Covid patients, for reasons that aren’t yet clear. So progress is often quite slow. And it’s rare for POTS to completely go away even with treatment. It remains unclear whether patients with post-Covid POTS will follow similar recoveries to people with non-Covid POTS.
- It’s not known how many post-Covid patients may develop POTS. Outside of Covid, POTS is estimated to affect up to 1% of the world’s population, according to a 2018 study in the Journal of Internal Medicine. The disorder can affect men and women, but most POTS cases are diagnosed in women between the ages of 15 and 50.
- Johns Hopkins has run a POTS clinic program for more than three years. After seeing an increasing number of post-Covid patients with POTS-like symptoms, it decided to open a new clinic dedicated to them, says Tae Chung, director of the Johns Hopkins POTS clinic. Doctors elsewhere are also identifying more post-Covid patients with POTS-like symptoms and case reports are being published in medical literature.
- POTS is generally diagnosed with what’s called a tilt table test, which measures changes in heart rate when someone goes from lying down to upright. If heart rate increases by 30 beats a minute or more when patients stand and they have symptoms such as lightheadedness that is worse when standing and often disabling, they are believed to have POTS.
- Tracy Tobiczyk, a 46-year-old flight attendant in Brownstown, Mich., has been home on medical leave since contracting Covid in the spring. In July, she was admitted to the University of Michigan Medical Center after weeks of experiencing a skyrocketing heart rate even while resting. Doctors diagnosed her with POTS.
- Before Covid, Ms. Tobiczyk says she used to walk 4 to 5 miles every day. Now, she gets dizzy when she stands. She says she can’t sit up for more than an hour because of chest pain and shortness of breath, which she likens to feeling like she’s drowning. “It leaves me laying on the couch or laying in bed all the time because I can’t get up to do anything,” she says.
- After being diagnosed with POTS she started wearing compression stockings every day and an abdominal binder. A nurse comes to her house to give her sodium chloride infusions to help increase blood volume.
- She takes three medications: one to increase her blood pressure, a beta-blocker to reduce her heart rate, and a mild steroid. “With the three of them together at least now I can walk to the refrigerator and go to the bathroom,” she says.
- She has had two rounds of physical and occupational therapy but didn’t make much progress. “I would do it and then that night I will have debilitating fatigue,” she says. “My husband had to carry me upstairs. It’s a tiredness where I feel like I’m almost dead.”
- Now, she is working on trying to exercise with a bicycle attached to her couch and with wall stands and leg lifts for about 10 minutes or less a day. “I try so hard because I’m an athletic person,” she says. “Every day is a struggle.”
- Amro Stino is an assistant professor and co-director of the autonomic lab at the University of Michigan Medical School and one of Ms. Tobiczyk’s doctors. Dr. Stino says he’s seen about half-a-dozen post-Covid patients who have POTS, generally young women who were previously very active.
- Doctors caution that post-Covid patients need to get a complete work-up evaluating their heart and lungs before receiving a POTS diagnosis to rule out other conditions. If a patient has myocarditis, another common post-Covid condition, increasing salt and fluid intake could cause further heart damage by stressing the heart.
- Elevated heart rates also have other causes, including blood clots in the lung, which Covid has been linked to. “One of the reasons I’m creating a special clinic is to make sure these symptoms are not coming from other causes, especially from blood clots,” says Dr. Chung at Johns Hopkins.
- POTS recovery rates vary. A recent study out of Italy of 42 patients published in the International Journal of Environmental Research found that most patients showed some improvement in symptoms after two years but still have the condition. “It’s a chronic condition,” says Lauren Stiles, president of Dysautonomia International, a nonprofit group, and a research assistant professor of neurology at Stony Brook University School of Medicine. Some experts believe POTS may be autoimmune in some cases. Several studies have indicated that patients with POTS have antibodies that are attacking the autonomic nerves in the heart and blood vessels.
- Benjamin Levine, a professor of internal medicine at UT Southwestern and director of Texas Health Presbyterian’s Institute for Exercise and Environmental Medicine, developed the “Levine protocol,” an exercise intervention program for POTS patients.
- He thinks it might be premature to be diagnosing Covid patients with conditions like POTS so soon. Some athletes, for example, might instead be suffering from muscle atrophy and deconditioning caused by inactivity while convalescing from the virus. “It doesn’t mean they have POTS but they can certainly have a POTS-like physiology,” says Dr. Levine.
- Other experts say deconditioning may exacerbate symptoms but isn’t causing them. Brent Goodman is an autonomic neurologist who runs the autonomic laboratory at Mayo Clinic’s Scottsdale, Ariz., location. He is working on a report on six post-Covid patients who developed POTS.
- Although normally patients need to have six months of symptoms to be diagnosed with POTS, Dr. Goodman says the earlier treatment is started, the better the recovery. “In the real world, if we identify autonomic dysfunction 3 weeks from symptoms onset we’re going to treat it,” he says.
4. Vaccination against tuberculosis can reduce the spread of C19 and ease its course
- In the spring, scientists throughout the world were actively discussing whether there is a connection between vaccination against tuberculosis in early childhood and the mild course of the new coronavirus disease. However, at that time, statistics on patients with C19 were still insufficient to draw reliable conclusions. Medical doctors throughout the world are currently beginning to find important patterns that will help protect public health in the future.
- An analysis of statistical data was conducted by experts from St Petersburg University. It showed that the incidence of C19, the course of acute interstitial pneumonia caused by infection, and the mortality rate from it are associated with being vaccinated with bacilli Calmette-Guerin (BCG) according to the national vaccination schedule. The mortality rate turned out to be lower in those countries and areas where national vaccine immunisation programmes have taken place for a long time or continue today, especially if revaccinations were practiced. These countries are Finland, China, Japan, Korea, and also countries in Eastern Europe, Central and South Asia, Africa, and the former USSR. The figures are significantly higher where large-scale BCG vaccination has never been practiced or stopped more than 20 years ago, for example, in the USA, Italy, the Netherlands, Belgium, and Germany excluding the lands of the former East Germany.
- The authors of the paper are young researchers: Alina Petyaeva, a student at St Petersburg University and a laboratory assistant researcher; Iana Ivashkevich, a graduate of the online course of St Petersburg University in General Pathophysiology, who carries out research at the University; and a physician Liubov Kazacheuskaya. The article is written under the supervision of Leonid Churilov M.D., Ph.D., Deputy Head of the Laboratory of the Mosaic of Autoimmunity and Head of the Department of Pathology at St Petersburg University.
- ‘BCG vaccine in Russia is given once in a lifetime for newborns,’ said Iana Ivashkevich. ‘But it is the early and long-term influence of the vaccine strain on the developing immune system that provides an adjuvant effect – it enhances the body’s immune reaction to various antigens, including many infectious ones. An adjuvant is a substance that enhances immune responses in a non-specific manner. Many adjuvants also enhance autoimmune processes. But the BCG vaccine has properties that are uncharacteristic for most adjuvants: for example, it acts as an immune response-modulating agent, and also reduces the risk of some autoimmune diseases and lymphoid tumours. C19 can cause autoimmune complications, so the properties of BCG, which are so unusual for an adjuvant, can be of benefit in this regard. According to statistics, in countries practicing neonatal BCG vaccination, there has been an overall decrease in infant mortality.
- Revaccination is a renewed vaccination throughout life. For BCG It is now practiced by only four countries: Belarus, Kazakhstan, Turkmenistan, and Uzbekistan. It is important that the effect of trained immune system response is achieved if the BCG vaccine is given to an immature immune system, scientists are certain. ‘There is reason to believe that in adults and elderly people who were not vaccinated in early childhood, the effect of late vaccine administration will be significantly less,’ explained Leonid Churilov. ‘At the same time, there are research papers by scientists from the Netherlands, where BCG is not given in childhood. They indicate that BCG administration to adults does not worsen, and, perhaps, somewhat attenuates the course of the disease when infected with the new coronavirus.’
- As the authors of the article said, the BCG vaccine activates a local immune response on the mucous membranes. It is through them that acute respiratory disease caused by SARS-CoV-2 spreads. According to the scientists, the BCG vaccine serves as a trigger for a ‘trained’ immune system response that activates monocytes, macrophages and natural killer cells – that power in the non-antigen-specific protective rogrammes of the body. Also, gamma-interferon, produced after BCG vaccination, and other mediators may ultimately attenuate the course of C19.
- ‘The causative agent of the new coronavirus infection and BCG have common peptides, which means that induction of cross-immunity is possible. Large clinical trials of the BCG vaccine and trials of its use for the prevention of the new coronavirus infection are currently underway, for example, in the Netherlands and Australia,’ said Iana Ivashkevich. Additionally, the scientists explain that the viewpoint on the connection of BCG vaccine with a decrease in the spread of C19 and a less severe course of the disease is confirmed by studies of international research teams from the USA, Germany, Canada, India, and Iran.
5. Medicine-carriers made from human cells can cure lung infections
- Scientists used human white blood cell membranes to carry two drugs, an antibiotic and an anti-inflammatory, directly to infected lungs in mice.
- The nano-sized drug delivery method developed at Washington State University successfully treated both the bacterial growth and inflammation in the mice’s lungs. The study, recently published in Communications Biology, shows a potential new strategy for treating infectious diseases, including C19.
- “If a doctor simply gives two drugs to a patient, they don’t go directly to the lungs. They circulate in the whole body, so potentially there’s a lot of toxicity,” said Zhenjia Wang, the study’s corresponding author and an associate professor in WSU’s College of Pharmacy and Pharmaceutical Sciences. “Instead, we can load the two types of drugs into these vesicles that specifically target the lung inflammation.”
- Wang and his research team have developed a method to essentially peel the membrane from neutrophils, the most common type of white blood cells that lead the body’s immune system response. Once emptied, these membranes can be used as nanovesicles, tiny empty sacks only 100 to 200 nanometers wide, which scientists can then fill with medicine.
- These nanovesicles retain some of the properties of the original white blood cells, so when they are injected into a patient, they travel directly to the inflamed area just as the cells would normally, but these nanovesicles carry the medicines that the scientists implanted to attack the infection.
- In this study, first author Jin Gao, a WSU research associate, loaded the nanovesicles with an antibiotic and resolvinD1, an anti-inflammatory derived from Omega 3 fatty acids, to treat lungs infected by P. aeruginosa, a common potentially fatal pathogen patients can catch in hospital settings. The researchers used two drugs because lung infections often create two problems, the infection itself and inflammation created by a strong immune system response.
- Toxicity studies and clinical trials would have to be conducted before this method could be used in human patients, but this study provides evidence that the innovation works for lung inflammation. If the method is ultimately proven safe and effective for humans, Wang said the nanovesicles could be loaded with any type of drug to treat a range of infectious diseases, including C19.
- “I think it’s possible to translate this technology to help treat C19,” said Wang. “C19 is a virus, not a bacterial pathogen, but it also causes an inflammation response in the lung, so we could load an antiviral drug like remdesivir into the nanovesicle, and it would target that inflammation.”
F. Concerns & Unknowns
1. Kidney disease leading risk factor for being hospitalized with C19
- An analysis of Geisinger’s electronic health records has revealed chronic kidney disease to be the leading risk factor for hospitalization from C19.
- A team of Geisinger researchers studied the health records of 12,971 individuals who were tested for C19 within the Geisinger system between March 7 and May 19. Of this group, 1,604 were COVID-positive and 354 required hospitalization. The team analyzed the records for association between specific clinical conditions, including kidney, cardiovascular, respiratory and metabolic conditions, and C19 hospitalization.
- Overall, chronic kidney disease was most strongly associated with hospitalization, and C19 patients with end-stage renal disease were 11 times more likely to be admitted to the hospital than patients without kidney disease.
- The results were published in PLOS ONE.
- “Previous studies have identified a variety of health conditions associated with an increased risk of COVID-related hospitalization, including diabetes, heart failure, hypertension, and chronic kidney disease. What is significant here is the magnitude of the kidney disease-related risk,” said Alex Chang, M.D., Geisinger nephrologist and co-director of Geisinger’s Kidney Health Research Institute. “These findings highlight the need to prevent C19-related illness in patients with kidney disease and other high-risk conditions.”
- How underlying medical conditions increase the risk of C19-related complications is not yet fully clear; however, the study suggests that the physiological stress caused by an excessive inflammatory response to C19 infection could destabilize organs already weakened by chronic disease, or that organ injury from the virus could act as a “second-hit” to these organs.
- “Consistent with this hypothesis, kidney and heart are among the tissues with the highest expression of ACE2, a SARS-CoV-2 receptor,” the team wrote.
- While the sample size studied was relatively small, Geisinger’s resources as an integrated health system allowed for a fairly comprehensive analysis of available data.
- “Our team used a novel approach made possible by our extensive electronic health records, unique demographic data and integrated health system,” said Tooraj Mirshahi, Ph.D., associate professor for Geisinger’s Department of Molecular and Functional Genomics. “We were able to perform this study despite having a much lower number of C19 cases compared to large hospitals in metropolitan areas.”
2. Could COVID delirium bring on dementia?
- In her job as a physician at the Boston Medical Center in Massachusetts, Sondra Crosby treated some of the first people in her region to get C19. So when she began feeling sick in April, Crosby wasn’t surprised to learn that she, too, had been infected. At first, her symptoms felt like those of a bad cold, but by the next day, she was too sick to get out of bed. She struggled to eat and depended on her husband to bring her sports drinks and fever-reducing medicine. Then she lost track of time completely.
- For five days, Crosby lay in a confused haze, unable to remember the simplest things, such as how to turn on her phone or what her address was. She began hallucinating, seeing lizards on her walls and smelling a repugnant reptilian odour. Only later did Crosby realize that she had had delirium, the formal medical term for her abrupt, severe disorientation.
- “I didn’t really start processing it until later when I started to come out of it,” she says. “I didn’t have the presence of mind to think that I was anything more than just sick and dehydrated.”
- Physicians treating people hospitalized with C19 report that a large number experience delirium, and that the condition disproportionately affects older adults. An April 2020 study in Strasbourg, France, found that 65% of people who were severely ill with coronavirus had acute confusion — a symptom of delirium1. Data presented last month at the annual meeting of the American College of Chest Physicians by scientists at the Vanderbilt University Medical Center in Nashville, Tennessee, showed that 55% of the 2,000 people they tracked who were treated for C19 in intensive-care units (ICUs) around the world had developed delirium. These numbers are much higher than doctors are used to: usually, about one-third of people who are critically ill develop delirium, according to a 2015 meta-analysis2 (see ‘How common is delirium?’).
- Delirium is so common in C19 that some researchers have proposed making the condition one of the disease’s diagnostic criteria. The pandemic has sparked physicians’ interest in the condition, says Sharon Inouye, a geriatrician at the Marcus Institute for Aging and Harvard Medical School in Boston, who has studied delirium for more than 30 years.
- As clinicians face the immediate realities of confusion and agitation on their wards, Inouye and other researchers are concerned about the future. In the past decade, long-term studies have revealed that a single episode of delirium can increase the risk of developing dementia years later3, and accelerate rates of cognitive decline in those who already have the condition4. The reverse is also true: having dementia makes someone more likely to develop delirium3. A set of simple steps, such as ensuring a family member is present to help people orient themselves, can reduce the incidence of delirium by 40%, but doctors struggle to follow that advice on C19 wards.
- But the links between delirium and dementia have been difficult to untangle: researchers need to follow patients for years to get results. The surge in people with delirium produced by the pandemic has focused attention on the condition and provided scientists with a unique opportunity to follow patients and determine if and how delirium might affect long-term cognition. Researchers have launched several studies to explore the long-term neurocognitive impacts of C19, including dementia, and Inouye and others hope that this work will allow researchers to explore the links between the two conditions in real time.
- If the pandemic can be said to have a silver lining, says Inouye, it has been to spur interest in how delirium can lead to dementia — and vice versa. What’s more, says Catherine Price, a neuropsychologist at the University of Florida in Gainesville, the spread of C19 “has highlighted the blurring of the lines between delirium and dementia, especially with more older adults in our populace”.
- Inouye’s interest in delirium began when she landed her first job as an internal-medicine physician at a Veterans Administration hospital in Connecticut in 1985. In her first month there, she treated more than 40 people for a variety of conditions. Six of them developed delirium during their stay; none seemed to return to their previous level of physical and mental health. To Inouye, the connection between her patients’ delirium and their poor prognosis was obvious. When she confessed her suspicions to her bosses, however, they just shrugged. Their attitude, Inouye says, was that delirium was just one of those things that happened.
- “Why is it okay for older adults to come into the hospital and lose their minds?” Inouye asked. Answering this question, she says, would be “an uphill battle my entire career”.
- Shortly after, she began a two-year fellowship to study the condition in depth. Her work showed that delirium occurs when several stressors converge. Pre-existing vulnerabilities such as chronic disease or cognitive impairment can combine with precipitating factors including surgery, anaesthesia or overwhelming infection to cause a sudden onset of confusion, disorientation and attention difficulties, especially in older adults5.
- “Delirium easily occurs when the brain is unable to compensate for a stressful situation,” explains Tino Emanuele Poloni, a neurologist at the Golgi Cenci Foundation outside Milan, Italy. Researchers think that the underlying biological causes are inflammation and an imbalance in neurotransmitters — chemical messengers such as dopamine and acetylcholine.
- Inouye’s mounting clinical experience has taught her that regardless of what precipitates delirium, around 70% of those with symptoms eventually recover completely. In the 30% who don’t, however, an episode of delirium predicts a downward spiral over a period of months that leads to profound cognitive impairment, even to symptoms of dementia.
- More-formal studies have reinforced the link, to varying degrees. Inouye investigated a group of 560 people aged 70 or older who had undergone surgery, and saw that cognitive decline over the subsequent 36 months was three times faster in those who developed delirium than in those who did not have the condition. A 2020 meta-analysis of 23 studies showed that delirium during a hospital stay was associated with 2.3 times greater odds of developing dementia. And work by a team of Brazilian scientists showed that, in a group of 309 people with an average age of 78 years, 32% of those who developed delirium in hospital progressed to having dementia, compared with just 16% of those who did not become delirious (see ‘Delirium and cognitive decline’).
- What’s more, the longer a person is delirious, the greater their risk of subsequent cognitive impairment, according to a 2013 study by psychologist James Jackson at Vanderbilt University, and his colleagues. Work by Inouye, Jackson, and other researchers found that the reverse was also true: even after controlling for age, existing dementia symptoms increased the chances of developing delirium.
- Scientists still don’t agree whether the link between delirium and dementia is strong only in those who would have developed dementia anyway, or whether delirium increases the risk of cognitive decline even in individuals who are not predisposed to it. Nor can they say precisely what it is about delirium that could provoke dementia. If researchers could identify these connections, then perhaps they could prevent delirium from escalating into dementia.
- “We don’t understand the mechanisms of delirium at all — we really don’t. And there is no successful management of delirium from a pharmaceutical standpoint,” Price says.
- Scientists have developed three hypotheses to explain how delirium might provoke dementia. One line of thinking holds that an accumulation of toxic cellular trash in the brain could cause short-term delirium and lead to longer-term damage. The body usually clears this molecular rubbish by way of the bloodstream and the glymphatic system, which is a network of channels filled with cerebrospinal fluid. Damage to vessels from an acute episode of delirium could persist and trigger dementia, or a brain that experiences delirium could become more prone to vascular problems in future.
- The second suspect is inflammation, which often troubles people who are hospitalized for infections, respiratory distress or cardiovascular disease. Surgery and severe infections can cause a build-up of cellular detritus in the brain, which triggers more inflammation. This short-term, all-hands-on-deck reaction safeguards the brain because it clears the harmful debris and the inflammation ultimately dies down. That is not the case for those who develop delirium, Inouye says. Persistent inflammation can trigger an acute episode of delirium, and cause neurons and associated cells, such as astrocytes and microglia, to deteriorate, leading to cognitive damage.
- The third idea is what’s known as the threshold hypothesis. Someone with dementia (even in the earliest stages) has fewer connections between neurons, and can show damage to the insulation that wraps them and helps convey signals — known as white matter. This loss strips the neurological reserves that help the person to cope with inflammation or infection, throwing them over the edge not just into delirium but into a more advanced dementia.
- Even though the genesis of delirium and its molecular connections to dementia remain unknown, Inouye has managed to find a way to cut rates of delirium in the hospital. She created a programme of simple strategies known as HELP (Hospital Elder Life Programme), which focus on reducing sedation, even during mechanical ventilation, paying close attention to nutrition and hydration, and ensuring the presence of family members to help reassure and orient patients. A 2015 meta-analysis10 showed that these steps reduced delirium by around 40%. Hospitals around the United States began instituting these simple protocols. Then C19 struck and made this all but impossible.
- As Crosby endured coronavirus-induced delirium in her Boston bedroom, Poloni was treating delirious people with C19 in Lombardy — Italy’s ground zero for the coronavirus. Many of Poloni’s patients already had dementia and, like many physicians, he was watching for common symptoms of respiratory infections such as fever, cough and difficulty breathing.
- But some of his patients didn’t show those signs at all. Instead, they mostly became “dull and sleepy”, Poloni said. Others became restless and agitated — all signs of delirium. It was so prominent that Poloni argued that delirium should be added to the virus’s diagnostic criteria. Inouye has made that argument, too, and it is supported by a study she published last month showing that 28% of older adults with C19 have delirium when they present to the emergency department.
- The high numbers of people who developed delirium immediately made Inouye, Price and other researchers worry that the pandemic could lead to a surge in dementia cases in the coming decades, on top of the increase in cases as a result of ageing populations (see ‘The cost of delirium’). “Is there going to be an increase in dementia from people who had C19 during adulthood or midlife?” asks Natalie Tronson, a neuropsychologist at the University of Michigan in Ann Arbor. “What happens over the next decades, as the population ages more?”
- To begin to find answers, institutes around the world have funded a variety of studies into the long-term cognitive effects of C19, some of which will look at delirium. Already under way in the United States is a study tracking people who have been treated in hospital for C19, many of whom developed delirium during their stay. This study will measure cognitive and psychiatric function in people participating in a trial to assess the safety and efficacy of hydroxychloroquine to treat coronavirus.
- An international study is planned to measure the prevalence of delirium in people with C19 in ICUs, as well as identifying factors that predict long-term outcomes. A separate study in Germany and the United Kingdom is also tracking neurocognitive outcomes in people with C19 to determine how delirium affects brain function months later. Another research project led by a team at Vanderbilt University is looking for an alternative to commonly-used sedatives such as benzodiazepines, which are known to increase delirium. The researchers are testing a sedative called dexmedetomidine to see whether it is a safer option for people hospitalized with C19.
- Inouye and Tronson hope that the funding of these long-term studies will lead to ongoing scientific interest in the delirium–dementia connection, and provide some insight.
- “It’s going to be, I think, a little bit frightening and a little bit enlightening, both about how illness affects dementia risk, but also what other lifestyle and genetic protective factors can influence risk as well,” Tronson says. “We’re learning quickly, but there’s still a lot of black boxes.”
3. “We can only speculate”: The miraculous Swiss C19 turnaround
All intensive care beds occupied
- Just a week ago, Switzerland was considered Europe’s big corona problem child. Now, however, the Swiss curve is pointing steeply downwards – although politicians have not adopted any major measures. Even experts are baffled.
- Switzerland opted for the middle ground: the country opted for a corona policy between Sweden’s former laissez-faire model and a tough lockdown strategy. Until mid-November it still looked as if Switzerland would fail miserably. But since mid-November there has been a clear downward movement in the curve.
- From over 10,000 new corona infections per day at the beginning of November, the number has now dropped to 4,500. And that without any restrictions having been adopted to contain the pandemic. The Federal Council has not tightened the measures since October 29.
- At a media conference on Tuesday, Martin Ackermann, President of the Swiss scientific Covid Taskforce, said the country was on the right track to contain the coronavirus . The task force expects the number of cases to actually halve about every two weeks. “The first stage goal has been reached,” said Ackermann.
Easy breathing for intensive care physicians
- This gives intensive care physicians in particular a sigh of relief. The “Swiss Society for Intensive Care Medicine” (SGI) reported Tuesday last week that all 876 intensive care beds in Switzerland were “currently practically fully occupied”. The national medical association even called on people who are particularly at risk from the coronavirus to consider drawing up a living will.
- Now the situation has eased a little. The number of patients who have to be treated in the intensive care unit has stabilized. “Currently there are still 260 free beds in the intensive care units,” said Virginie Masserey from the Federal Office of Public Health (BAG) on Tuesday.
Success despite “half-hearted measures”
- But why did the numbers fall so rapidly, despite open restaurants, shops and lax contact bans? The experts don’t really know that either. At the moment it is “from a scientific point of view still too early to judge”, says the Swiss epidemiologist Marcel Salathé to FOCUS Online. And also Antje Heise, intensive care physician and president of the medical profession of the SGI, told the “Welt” : “We can only speculate about what the turnaround in the number of infections resulted in.”
- So whether the Swiss middle ground is the reason that the number of new corona infections is falling again is uncertain. There was criticism of the strategy from many medical professionals in particular: The loose corona policy only brought the country into the situation. There were great doubts as to whether the measures would be enough to keep the health system from collapsing. For example, Isabella Eckerle, a virologist at the University Clinics in Geneva, tweeted last week that the full intensive care beds were the result of “a lack of infection control and delayed and half-hearted measures”.
“The level is still very high”
- Nevertheless, Professor Salathé has not given the all-clear: “I am not yet ready to speak of a relatively normalized situation, and even if this is the case, it will take some time before we understand what has worked how well,” estimates he the situation.
- And Rudolf Hauri, President of the Association of Swiss Cantonal Doctors, advised the SRF to be cautious: “You can only speak of relaxation when the number of cases has dropped significantly and sustainably. The level is still very high overall, with regional differences, ”says Hauri.
- The second wave was significantly more fatal in Switzerland than the first, in which the country still relied on a strict lockdown strategy. Just last Monday, Switzerland reached the highest number of deaths since the beginning of the pandemic: The John Hopkins University counted 167 deaths in connection with C19 . On Thursday, the number of corona deaths since the previous day was 116. Although the number has fallen, it is still very high based on the low population density. The Swiss tabloid “Blick” According to the excess mortality was stronger than in the first wave. The newspaper’s grim conclusion: “And it will be with us for a long time.”
4. C19 Likely Began in U.S. in Mid-December 2019
- The new coronavirus infected people in the U.S. in mid-December 2019, a few weeks before it was officially identified in China and about a month earlier than public health authorities found the first U.S. case, according to a government study published Monday.
- The findings significantly strengthen evidence suggesting the virus was spreading around the world well before public health authorities and researchers became aware, upending initial thinking about how early and quickly it emerged.
- Scientists at the U.S. Centers for Disease Control and Prevention found evidence of infection in 106 of 7,389 blood donations collected by the American Red Cross from residents in nine states across the U.S., according to the study published online in the journal Clinical Infectious Diseases.
- The scientists based their study on blood samples that the American Red Cross collected between Dec. 13 and Jan. 17 and later sent to the CDC for testing to see if any had antibodies to the new coronavirus, which is named SARS-CoV-2.
- “SARS-CoV-2 infections may have been present in the U.S. in December 2019, earlier than previously recognized,” the authors wrote.
- A person’s immune system develops antibodies when exposed to a pathogen like a virus to fight it off. Their presence suggests exposure to a virus.
- In analyzing the blood samples, the CDC scientists found antibodies in 39 samples from California, Oregon and Washington state collected between Dec. 13 and Dec. 16.
- The findings suggest there were isolated cases of coronavirus infection on the U.S. West Coast in mid-December, the scientists wrote.
- They also found 67 samples with antibodies in Massachusetts, Michigan, Wisconsin or Iowa, and Connecticut or Rhode Island collected between Dec. 30 and Jan. 17.
- The scientists said they ruled out the possibility that the antibodies they found had developed to fight off other coronaviruses, which cause the common cold. They did that by looking for antibodies specific to the new coronavirus in 90 of the samples.
- They said they found antibodies specific to SARS-CoV-2 in 84 of the samples, or nearly all of them.
- The results add to growing evidence suggesting C19 was present outside of China earlier than previously known. Researchers found the virus, for example, in a retrospective analysis of a specimen from a patient who was hospitalized in France on Dec. 27, 2019.
- The first C19 case in the U.S. was reported on Jan. 19, two days after testing for the virus began there, the CDC researchers said. A young man returning from China a few days earlier suspected he might have the disease and sought care for his symptoms.
- Two other people who were subsequently diagnosed in the U.S. also developed symptoms in mid-January.
- Earlier studies have also suggested that C19 had moved beyond just isolated cases and was spreading in communities in the U.S. by mid- to late-January, though epidemiologists say that the virus likely didn’t circulate widely in communities until later in February.
- The new study shows the value of screening routinely collected blood samples for evidence of viruses spreading in a population, the CDC authors said, adding that the agency is continuing to conduct surveillance for C19 this way.
- Not only did C19 likely appear in the U.S. earlier than previously known, but researchers have found evidence that the virus is far more widespread in the U.S. than testing indicates.
- Some 53 million people in the U.S. likely had contracted C19 by the end of September, according to a modeling estimate published last week by CDC researchers. Roughly 6.9 million infections had been confirmed within that time period, suggesting that roughly one in every eight cases was identified.
- Yet, the majority of the U.S. population hasn’t been infected. On Nov. 24, a CDC study published in the journal JAMA Internal Medicine estimated that fewer than 1% to 23% of people in the U.S. had antibodies, depending on the location.
5. How a Bidding War for C19 Nurses Hurts the Pandemic Response
- In March, Claire Tripeny was watching her dream job fall apart. She’d been working as an intensive care nurse at St. Anthony Hospital in Lakewood, Colorado, and loved it, despite the mediocre pay typical for the region. But when C19 hit, that calculation changed.
- She remembers her employers telling her and her colleagues to “suck it up” as they struggled to care for six patients each and patched their protective gear with tape until it fully fell apart. The $800 or so a week she took home no longer felt worth it.
- “I was not sleeping and having the most anxiety in my life,” said Tripeny. “I’m like, ‘I’m gonna go where my skills are needed and I can be guaranteed that I have the protection I need.’”
- In April, she packed her bags for a two-month contract in then-Covid hot spot New Jersey, as part of what she called a “mass exodus” of nurses leaving the suburban Denver hospital to become traveling nurses. Her new pay? About $5,200 a week, and with a contract that required adequate protective gear.
- Months later, the offerings — and the stakes — are even higher for nurses willing to move. In Sioux Falls, South Dakota, nurses can make more than $6,200 a week. A recent posting for a job in Fargo, North Dakota, offered more than $8,000 a week. Some can get as much as $10,000.
- Early in the pandemic, hospitals were competing for ventilators, Covid tests and personal protective equipment. Now, sites across the country are competing for nurses. The fall surge in Covid cases has turned hospital staffing into a sort of national bidding war, with hospitals willing to pay exorbitant wages to secure the nurses they need. That threatens to shift the supply of nurses toward more affluent areas, leaving rural and urban public hospitals short-staffed as the pandemic worsens, and some hospitals unable to care for critically ill patients.
- “That is a huge threat,” said Angelina Salazar, CEO of the Western Healthcare Alliance, a consortium of 29 small hospitals in rural Colorado and Utah. “There’s no way rural hospitals can afford to pay that kind of salary.”
- “I’m like, ‘I’m gonna go where my skills are needed and I can be guaranteed that I have the protection I need,’” said Tripeny.
- Hospitals have long relied on traveling nurses to fill gaps in staffing without committing to long-term hiring. Early in the pandemic, doctors and nurses traveled from unaffected areas to hot spots like California, Washington state and New York to help with regional surges. But now, with virtually every part of the country experiencing a surge — infecting medical professionals in the process — the competition for the finite number of available nurses is becoming more intense.
- “We all thought, ‘Well, when it’s Colorado’s turn, we’ll draw on the same resources; we’ll call our surrounding states and they’ll send help,’” said Julie Lonborg, a spokesperson for the Colorado Hospital Association. “Now it’s a national outbreak. It’s not just one or two spots, as it was in the spring. It’s really significant across the country, which means everybody is looking for those resources.”
- In North Dakota, Tessa Johnson said she’s getting multiple messages a day on LinkedIn from headhunters. Johnson, president of the North Dakota Nurses Association, said the pandemic appears to be hastening a brain drain of nurses there. She suspects more nurses may choose to leave or retire early after North Dakota Gov. Doug Burgum told health care workers they could stay on the job even if they’ve tested positive for C19.
- All four of Utah’s major health care systems have seen nurses leave for traveling nurse positions, said Jordan Sorenson, a project manager for the Utah Hospital Association.
- “Nurses quit, join traveling nursing companies and go work for a different hospital down the street, making two to three times the rate,” he said. “So, it’s really a kind of a rob-Peter-to-pay-Paul staffing situation.”
- Hospitals not only pay the higher salaries offered to traveling nurses but also pay a commission to the traveling nurse agency, Sorenson said. Utah hospitals are trying to avoid hiring away nurses from other hospitals within the state. Hiring from a neighboring state like Colorado, though, could mean Colorado hospitals would poach from Utah.
- “In the wake of the current spike in Covid hospitalizations, calling the labor market for registered nurses ‘cutthroat’ is an understatement,” said Adam Seth Litwin, an associate professor of industrial and labor relations at Cornell University. “Even if the health care sector can somehow find more beds, it cannot just go out and buy more front-line caregivers.”
- Litwin said he’s glad to see the labor market rewarding essential workers — disproportionately women and people of color — with higher wages. Under normal circumstances, allowing markets to determine where people will work and for what pay is ideal.
- “On the other hand, we are not operating under normal circumstances,” he said. “In the midst of a severe public health crisis, I worry that the individual incentives facing hospitals on the one side and individual RNs on the other conflict sharply with the needs of society as whole.”
- Some hospitals are exploring ways to overcome staffing challenges without blowing the budget. That could include changing nurse-to-patient ratios, although that would likely affect patient care. In Utah, the hospital association has talked with the state nursing board about allowing nursing students in their final year of training to be certified early.
- In 2018, according to data from a national survey, about 31,000 traveling nurses worked nationwide. Now, Deane estimated, there are at least 50,000 travel nurses. Deane, who calls travel nurses “superheroes,” suspects a lot of them are postoperative nurses who were laid off when their hospitals stopped doing elective surgeries during the first lockdowns.
- “We’ve sent nurses to Aruba, the Bahamas and Curacao because they’ve needed help with Covid,” said Deane. “You’re going down there, you’re making $5,000 a week and all your expenses are paid, right? Who’s not gonna say yes?”
- Krucial Staffing specializes in sending health care workers to disaster locations, using military-style logistics. It filled hotels and rented dozens of buses to get nurses to hot spots in New York and Texas. CEO Brian Cleary said that, since the pandemic started, the company has grown its administrative staff from 12 to more than 200.
- “Right now we’re at our highest volume we’ve been,” said Cleary, who added that over Halloween weekend alone about 1,000 nurses joined the roster of “reservists.”
- With a base rate of $95 an hour, he said, some nurses working overtime end up coming away with $10,000 a week, though there are downsides, like the fact that the gig doesn’t come with health insurance and it’s an unstable, boom-and-bust market.
G. The Road Back?
1. Majorities of people support restrictive measures to curb C19 spread
- Six in 10 people across all 50 U.S. states support a combination of restrictive measures to curb the spread of C19, according to a new survey from the Covid States Project.
- Nearly 20,000 people were surveyed between Nov. 3-23 about their views on seven measures to help stop the spread of the pandemic, including restricting travel and large gatherings, and 60% or more supported all seven measures.
- Large majorities in every state supported five of the seven measures, the exceptions being prohibiting in-person K-12 instruction and closing nonessential businesses.
- Across the board — including across party lines — people were least supportive of closing businesses beyond pharmacies and grocery stores.
- Read the survey here
Source: Covid States Project
H. Back to School!?
1. University reopenings tied to some C19 spikes
- University communities outside of heavily populated areas may be particularly vulnerable to C19 transmission from student influxes.
- Researchers analyzed the impact of reopening U.S. universities with at least 15,000 students in the fall 2020 semester in 80 counties with at least 1 million residents, 49 counties with 250,000 to 999,999 residents, and 44 counties with up to 249,999 residents.
- Reopenings were linked with “dramatic” C19 spikes in counties with fewer than 250,000 residents, whereas larger counties, “had a flat infection growth rate,” according to Mike Penuliar of Texas Tech University.
- Infection rates in the counties that experienced spikes never returned to pre-reopening levels, his team reported on Sunday on medRxiv ahead of peer review. “Spikes in rural locations can be dire,” Penuliar said, noting fewer hospital resources, intensive care unit beds and expert medical personnel in those areas.
- Coauthor Billy Philips, also of Texas Tech, added that much of the fall surges in this study can be attributed to a vulnerable pool of people in the general population being infected by college students who are more likely to have mild or asymptomatic disease and unwittingly spread the virus.
2. School closures have cost an estimated 5.5 million years of life lost
- Based on the current understanding of the associations between school disruption and decreased educational attainment and between decreased educational attainment and lower life expectancy, is it possible to estimate the association between school closure during the coronavirus disease 2019 pandemic and decreased life expectancy of publicly educated primary school–aged children in the United States?
- This decision analytical model found that missed instruction during 2020 could be associated with an estimated 5.53 million years of life lost. This loss in life expectancy was likely to be greater than would have been observed if leaving primary schools open had led to an expansion of the first wave of the pandemic.
- These findings suggest that the decision to close US public primary schools in the early months of 2020 may be associated with a decrease in life expectancy for US children.
- United States primary school closures during the 2020 coronavirus disease 2019 (C19) pandemic affected millions of children, with little understanding of the potential health outcomes associated with educational disruption.
- To estimate the potential years of life lost (YLL) associated with the C19 pandemic conditioned on primary schools being closed or remaining open.
- This decision analytical model estimated the association between school closures and reduced educational attainment and the association between reduced educational attainment and life expectancy using publicly available data sources, including data for 2020 from the US Centers for Disease Control and Prevention, the US Social Security Administration, and the US Census Bureau. Direct C19 mortality and potential increases in mortality that might have resulted if school opening led to increased transmission of C19 were also estimated.
Main Outcomes and Measures
- A total of 24.2 million children aged 5 to 11 years attended public schools that were closed during the 2020 pandemic, losing a median of 54 (interquartile range, 48-62.5) days of instruction. Missed instruction was associated with a mean loss of 0.31 years of final educational attainment for boys and 0.21 years for girls. Summed across the population, an estimated 5.53 million YLL may be associated with school closures. The Centers for Disease Control and Prevention reported a total of 88, 241 US deaths from C19 through the end of May 2020, with an estimated 1.50 million YLL as a result.
- Had schools remained open, 1.47 million additional YLL could have been expected as a result, based on results of studies associating school closure with decreased pandemic spread. Comparing the full distributions of estimated YLL under both “schools open” and “schools closed” conditions, the analysis observed a 98.1% probability that school opening would have been associated with a lower total YLL than school closure.
Conclusions and Relevance
- In this decision analytical model of years of life potentially lost under differing conditions of school closure, the analysis favored schools remaining open. Future decisions regarding school closures during the pandemic should consider the association between educational disruption and decreased expected lifespan and give greater weight to the potential outcomes of school closure on children’s health.
I. Projections & Our (Possible) Future
1. New Dynamic Global COVID Surveillance System Predicts Direction, Speed and Acceleration of Virus
- A new C19 global surveillance system has been developed which can dynamically track not just where the virus is now, but where it is going, how fast it will arrive and whether that speed is accelerating.
- The new surveillance system, the first to dynamically track the virus, is being rolled out in 195 countries. It also will dynamically track the virus in individual U.S. states and metropolitan areas and in Canadian provinces.
- “Now we can easily identify outbreaks at their beginning,” said Lori Post, the lead investigator and director of the Buehler Center for Health Policy and Economics at Northwestern University Feinberg School of Medicine. “You want to know where the pandemic is accelerating, how fast it is moving and how that compares to prior weeks.”
- Post, James Oehmke of Northwestern, and Charles Moss of the University of Florida worked day and night over the past four months to develop the novel surveillance system, based on path-breaking research led by Oehmke.
- “We can inform leaders where the outbreak is occurring before it shows up in overcrowded hospitals and morgues,” Post said. “Current systems are static and ours is dynamic.”
- Northwestern is hosting a dashboard for the new COVID tracking system — open to anyone — with the new metrics as well as traditional metrics. Each country’s dashboard will be monitored in every U.S. embassy in the world to inform policy leaders around the globe. Users will have metrics of the whole world at their fingertips.
- The new system and the first U.S. surveillance report has bee published in the Journal of Medical Internet Research.
- The global surveillance app analyzes the virus in the same way the field of economics measures the expansion and contraction of the economy.
- “These methods are tried and tested, but this is the first time they are being applied to disease surveillance,” Post said. “We had the model and metrics validated for medical surveillance and published. We know they work.”
- The project is named GASSP (GlobAl Sars-Co2 Surveillance Project).
- Existing surveillance can’t identify pandemic shifts or signal a coming outbreak.
- Existing surveillance, which hasn’t changed much in 50 years, measures the caseload in terms of new and cumulative deaths and infections. They don’t identify significant shifts in the pandemic or sound the alarm when there is concerning acceleration of disease transmission signaling an outbreak.
- The surveillance system can help U.S. embassies and missions support partnering countries to formulate and implement policies that mitigate C19 or adverse outcomes such as food insecurity, and understand which policies are working best.
- These new metrics also can help developed countries and their health systems prepare for swift changes in the pandemic.
- “For example, relative to other countries, the Netherlands is a small country and doesn’t have the same caseload as some larger countries like Spain,” Post said, “But they have alarming signs right now — increased speed, acceleration and positive jerk and that means potential for explosive growth.”
Drilling down to county level to save state economies
- In the U.S., if the pulse of one state is bad, the surveillance can drill down into the county level to identify where the problem is originating from. This would enable only the troubled areas to be under strict quarantine masking rules to preserve the state economy, Post said.
- Among the surveillance system’s many findings in the U.S., the surveillance system reports:
- Hawaii, Vermont and Maine have the smallest rate of new daily infections per 100,000 population, but because their speed is accelerating and their persistence remains positive, they need to enforce masking, social distancing, crowd control and hygiene or they could potentially escalate into explosive growth.
- Wisconsin is a state where the outbreak will likely continue to explode. Wisconsin and California have similar average number of new COVID cases per day with California 6.8 times bigger than Wisconsin. Wisconsin is disproportionately affected by the pandemic, and yet it was California that declared an emergency stay-at-home order.
- Wyoming has several indicators over the past three weeks indicating their outbreak is going to get much worse.
Speed isn’t enough, why acceleration and jerk matter
- “Speed itself doesn’t tell us enough,” Post said. “We have to know the acceleration and how that compares week to week — jerk — to be prepared for what’s coming in the pandemic.”
- Jerk is a measure of increasing acceleration and may help predict the stress the pandemic will place on health care systems. “Jerk can help turn a reactive policy response into a proactive policy response,” said Oehmke, adjunct professor of emergency medicine at Northwestern. Jerk is a physics term, Oehmke said, because until now the concept did not exist in the public health nomenclature.
- “If you are the governor of New York, it is not helpful to prevent future outbreaks by looking at how many people already were infected by the novel coronavirus,” Post said. “You want to know what is going on now and what are likely scenarios in the near future. By looking at speed, acceleration, and jerk, we can inform leaders where the outbreak is occurring before it shows up in overcrowded hospitals and morgues.”
- The system also controls for incomplete data using state-of-the-art statistical methods. Existing surveillance picks up severe cases, Post said, so in the case of COVID, those numbers likely only represent 10% to 20% of caseload.
“We are like air traffic controllers”
- “We are picking up the dynamic characteristics of the pandemic,” Post said. “Pandemics move around and change. We are like air traffic controllers guiding in an airplane during a thunderstorm. The pilot can’t see. They don’t know where to go — they need information. We have to guide that plane on instruments. Analogously, we need to inform public health leaders when there are significant shifts to the pandemic.”
- Persistence — an echo effect forward — is equally important to pandemic surveillance.
- “The persistence effect measures the likelihood people newly presenting last week infected others who will present with C19 this week, who are infecting others who will present next week, and so on,” Oehmke said. “To flatten the curve and end the pandemic, we need to reduce the persistence effect and eventually bring it to zero — that has to be a key policy objective.”
- While persistence effects are known in financial market analysis, their application to pandemics is new.
- The researchers have written papers about the C19 pandemic from 12 global regions of the world. Two foundational papers published in JMIR analyzed U.S. data, then surveillance papers analyzed sub-Sahara Africa, South Asia, and now the third surveillance paper from the U.S.
- For developing countries included in the dashboard, analysis is funded by the U.S. Agency for International Development. Davee Innovations Research Endowment is funding developed nations’ surveillance.
J. Practical Tips & Other Useful Information
1. Do Vitamin D, Zinc, and Other Vitamins Protect Against C19?
- Dozens of studies are underway to determine whether supplements of common nutrients and vitamins could help ward off infections of the coronavirus (SARS-CoV-2), the coronavirus that causes C19, or even treat the disease by reducing the dangerous inflammation it causes in the lungs and other organs. A few have proven promising. But the research is not yet conclusive on any supplements, and it’s quite inconclusive for others. Meanwhile, scientists caution that too much of any nutrient can have negative side effects.
- The greatest benefit of supplements is likely for people who suffer specific nutrient deficiencies.
- “Deficiency in one of many essential nutrients can reduce the body’s immune defenses, and fixing these deficiencies with supplements will then be beneficial,” says Walter Willett, MD, a professor of epidemiology and nutrition at the Harvard T.H. Chan School of Public Health. “It doesn’t mean that continuing to increase intake [beyond the body’s needs] will have further benefit.”
- Think of a car missing a wheel. Replacing the fourth wheel will make the car work much better, Willett notes, but adding a fifth wheel won’t offer any additional benefit and can actually hamper performance. If you eat well and get enough vitamin D — more on that below — you likely have all the nutrients necessary to build a healthy immune system, and adding extra nutrients doesn’t make you extra healthy.
- But the vast majority of Americans don’t meet basic dietary guidelines. “I think it is reasonable for most people to take a multivitamin/multimineral supplement as a nutritional safety net,” Willett tells Elemental, adding that doing so was important for many people before Covid, “and it is more important now.” That holds true for both prevention and if you catch the disease. However, if you have C19, you should discuss any supplements or other treatments with a health care provider. And if you’re taking any medications or have any underlying health issues, it’s important to seek a physician’s advice on preventive supplements, too.
- Here are the handful of supplements under the most intense study for effectiveness against the coronavirus:
- The logic: Vitamin C is a known antioxidant that bolsters the immune system and, in general, helps prevent inflammation.
- General evidence: Vitamin C is thought to help protect against some viral and bacterial infections and lessen symptoms of infections, but evidence on the vitamin’s role even in preventing the common cold is often conflicting. A small study (167 patients) done before C19 existed found that vitamin C infusions during hospital care reduced mortality and cut down on ICU stays for people suffering severe acute respiratory failure and sepsis, which is a dangerous cascade of inflammation throughout the body triggered by an infection. Both of those conditions are leading causes of C19 death.
- C19 evidence: Vitamin C might help prevent C19 and also lessen the inflammatory reactions behind some severe C19 cases, according to a review of research on the topic published in the latest issue of the journal Nutrition. But the study authors state clearly that only clinical trials — at least a dozen of which are underway — would prove their suspicions.
- “We definitely don’t want to be deficient, but I am not optimistic about any benefit of higher doses,” Willett says.
- Dosage: U.S. Recommended Dietary Allowance (RDA) is 75 to 120 milligrams per day (toward the lower for most adults and the higher end for breastfeeding women).
- How to get some: Just eat your fruits and veggies and you’ll be fine. One cup of strawberries, red peppers, broccoli, or many other fruits or vegetables gives you all you need.
- Risks: While generally considered safe even in high doses, way too much vitamin C — anything above 2,000 milligrams daily—can cause headaches, insomnia, diarrhea, heartburn, and other issues.
- “I think it is reasonable for most people to take a multivitamin/multimineral supplement as a nutritional safety net, and it is more important now.”
- The logic: Vitamin D is known to help keep bones strong and might bolster the function of immune cells. It’s unusual among vitamins in that it’s rare in foods but is produced by sunlight in the skin and then converted to its usable form in the kidneys. Around 35% to 40% of U.S. adults are thought to have a vitamin D deficiency, and the rate is higher in Black people. However, there is no agreed-upon standard for what constitutes mild, moderate, or severe deficiency.
- General evidence: A 2019 review of existing clinical trials indicated vitamin D supplements can reduce the severity of acute respiratory tract infections in hospitalized patients.
- C19 evidence: A study early this year of 20 European countries found a link between low levels of vitamin D and higher percentages of C19 cases and mortality. Separately, more than 80% of 200 people hospitalized for C19 in Spain were found to be deficient in vitamin D, according to a study published in October in the Journal of Clinical Endocrinology & Metabolism.
- “Vitamin D treatment should be recommended in C19 patients with low levels of vitamin D circulating in the blood since this approach might have beneficial effects in both the musculoskeletal and the immune system,” said the Spanish study’s co-author, José Hernández, PhD, of the University of Cantabria in Spain. Neither study can say for sure that the deficiency causes the negative outcomes or whether other factors are involved — such as people with the deficiency having other underlying health conditions, or lacking health insurance or access to hospitals.
- Yet another study actually tested the effects of vitamin D on C19 patients by adding it to the treatment for one group and not another. Among 26 people who didn’t get the vitamin, half ended up in the intensive care unit and two died. Among the 50 people who got the vitamin, one went to ICU and none died. The results require follow-up research to be conclusive, the scientists wrote in the Journal of Steroid Biochemistry and Molecular Biology. Willett calls vitamin D the “most promising” supplement under study for Covid protection.
- Dosage: The U.S. Recommended Dietary Allowance (RDA) for adults is 600 IU (international units) daily. But there’s no firm agreement on this. “I think 2,000 to 4,000 IU per day will get most people out of the deficiency zone and is safe,” Willett says.
- How to get some: About 20 minutes of daily sunshine on 40% of exposed skin produces ample vitamin D in general, but such estimates are gross generalities. Dark-skinned people need more exposure to produce the same amount of the vitamin.
- Food sources: Salmon (444 IU in three ounces) and other oily fish are excellent sources, as are eggs (44 IU per egg), along with fortified foods including milk and some cereals. If you don’t get out much or don’t have an ideal diet, then: “I think it is reasonable for most people, especially if they have darker skin, to take a [vitamin D] supplement,” Willett says. Note, however, that if you choose a multivitamin, your D-vitamin needs may be covered, so be careful not to let the total exceed 4,000 IU.
- Risks: Too much exposure to sun, particularly during midday and especially if it causes sunburns, raises the risk of skin cancer. Excess vitamin D via supplements — anything over 4,000 IU, increases the risk of reversing the beneficial effects, including upping the odds of bone fractures. In rare cases, way too much can be outright toxic.
- The logic: Melatonin is a powerful hormone whose production is triggered in the brain by darkness, signaling sleep time. It also supports a healthy immune system directly, and the sleep it promotes is key to a strong immune system. Lack of time outside in bright daylight — a common modern issue — confuses the brain’s biological clock, reducing melatonin production.
- General evidence: An overview of immune system benefits from melatonin supplements, published last year in the journal Cell Death & Disease, touted its powerful antioxidant properties and anti-inflammatory effects. In a study of mice in the Journal of Functional Foods, scientists found “the anti-inflammatory and immune-modulatory effects of melatonin may provide a beneficial effect” in treating influenza, which like C19 is primarily a respiratory disease. The role of naturally produced melatonin in sleep is vital, and sleep loss — for just one night and more over time — raises the risk of infections generally, much research finds. Specifically, it reduces the production of proteins and antibodies that fight infections.
- C19 evidence: Taking melatonin supplements was linked to a 30% reduction in the likelihood of testing positive for C19 in a November study of data from the Cleveland Clinic, published in the journal PLOS Biology. The reduction was 52% for Black people. Other evidence in the study suggests melatonin might also be effective in treating C19. “I think this data is interesting, but like much other SARS-CoV-2 data, it needs to be further validated with placebo-controlled, randomized controlled studies,” says Melissa Badowski, PharmD, an associate professor of infectious diseases at the University of Illinois at Chicago College of Pharmacy, who was not involved in the study. “We also do not know if these individuals were practicing mask-wearing, hand hygiene, or social distancing. I think there may be a signal, but a lot more research is needed to prove if this signal is valid or not.”
- Dosage: There is no federal RDA nor any formal advice on supplement dose ranges. Some countries treat melatonin as a drug rather than a dietary supplement and regulate it accordingly. If you take a supplement, be careful: Too much can cause daytime sleepiness. Ann Pressler, a nurse practitioner at the Cleveland Clinic, says 0.5 to three milligrams should be sufficient. Others advise up to five milligrams.
- How to get some: Being outside at least two hours in bright, natural light helps keep the body’s biological clock tuned up and on time, so it makes sufficient melatonin… in the late evening when it’s supposed to make you drowsy.
- Risks: Side effects of melatonin supplements include headache, dizziness, nausea, and drowsiness during the day, and in rarer cases anxiety, low blood pressure and other effects — especially in doses above 10 milligrams. It can interact negatively with some medications, including diabetes medicine. Also, the actual ingredients in some supplements, which are unregulated by the federal government, are notoriously unpredictable. A 2017 study found the melatonin content was off by more than 10% compared to what the labels claimed in 71% of 30 supplements analyzed, ranging from 83% less to nearly five times more.
- The logic: Zinc helps the body fight bacterial and viral infections. But most people get plenty of zinc in their diets (though vegetarians and people who drink a lot of alcohol may not). Despite being touted as a coronavirus treatment, it’s well behind the pack of other options above.
- General evidence: “Oral zinc supplements might benefit people with low levels of zinc,” according to the Mayo Clinic. “Taken soon after cold symptoms appear, zinc might also shorten the length of a cold.”
- C19 evidence: Clinical studies are underway to determine if zinc can help treat C19, but for now, “there are insufficient data to recommend either for or against the use of zinc for the treatment of C19,” the National Institutes of Health states.
- “This falls in the category of ‘necessary to avoid deficiency, but less promising in higher doses,’” Willett says.
- Dosage: Eight milligrams for women, 11 for men. A healthy, varied diet should provide all you need.
- How to get some: Oysters and other shellfish, red meat, and poultry are all good options. Other less-effective sources include beans, nuts, seeds, whole grains, and dairy. Cereals are often fortified with zinc.
- Risks: Short-term side effects of zinc supplements include indigestion, headache, and vomiting, and zinc can interfere with some drugs, including antibiotics, blood thinners, and some arthritis medications. Over time, too much zinc can cause copper deficiencies, blood diseases, and nerve damage.
How to maintain your immune system naturally
- The longer list of supplements and alternative remedies promoted for C19 prevention or treatment, without sustaining evidence nor much if any formal research, includes vitamins A and B, herbal teas, essential oils, oleander, tinctures, and colloidal silver.
- “There is no scientific evidence that any of these alternative remedies can prevent or cure C19,” states the National Center for Complementary and Integrative Health. “In fact, some of them may not be safe to consume.”
- The smartest bet is to take reasonable steps to maintain a healthy immune system by eating well and staying physically active, both of which promote better sleep, adding up to a trio of immunity benefits, says Suzanne Cassel, MD, an immunologist at Cedars-Sinai Medical Center. “You actually don’t want your immune system to be stronger, you want it to be balanced,” Cassel says. “Too much of an immune response is just as bad as too little response.”
- If you worry you might have a nutrient deficiency, consult a physician. Otherwise: “Wash your hands, wear a mask, and socially distance,” Badowski advises. “I would recommend this before turning to supplements that we are not sure actually work.”
2. Are C19 Bubbles a Good Idea?
- Americans’ social lifelines are beginning to fray. As the temperature drops and the gray twilight arrives earlier each day, comfortably mingling outside during the pandemic is getting more difficult across much of the country. For many people, it’s already impossible.
- To combat the loneliness of winter, some of us might be tempted to turn to pods, otherwise known as bubbles. The basic idea is that people who don’t live together can still spend time together indoors, as long as their pod stays small and exclusive. And pods aren’t just for the winter: Since March, parents have formed child-care bubbles. Third graders have been assigned to learning pods. Some NBA teams were in a bubble for months. A July survey of 1,000 Americans found that 47 percent said they were in a bubble.
- In theory, a bubble is meant to limit the spread of the coronavirus by trapping it in small groups of people and preventing it from jumping out. “The goal here with an infectious agent like SARS-CoV-2 is that you want to try and not give it hosts,” Keri Althoff, an epidemiologist at Johns Hopkins University, told me. “That’s the name of the game.” Earlier this year, researchers modeled the best ways to flatten the curve by limiting social interactions and found that having people interact with only the same few contacts over and over again was the most effective approach.
- But the details of how exactly to go about podding can be hard to pin down. The answers to some basic questions—how many people should be in a bubble? what’s okay for the members of a pod to do together?—are still unclear. For example, Beth McGraw, the director of the Center for Infectious Disease Dynamics at Penn State, suggests including 10 or fewer people who live in just a handful of households, but she and all of the experts I spoke with for this story emphasized that there’s no magic number that makes a group safe or unsafe.
- Bubbles might sound great—you can have your friends and your safety too!—but they don’t always work out the way they’re supposed to. Some pods are enormous. Some are open to an untold number of people’s germs through contacts of contacts (of contacts of contacts of contacts). “I think there’s leakage in a lot of people’s pods,” Whitney Robinson, an epidemiologist at the University of North Carolina, told me. Last week, a New York Times columnist examined the ties in his bubble and found that he was connected to more than 100 people—and that’s just whom he was able to trace.
- No public-health scheme is perfect, and we will need to layer as many of them as we can in order to survive the pandemic. But with pods, the country hasn’t even settled on a shared definition. If we do not reach a consensus on best bubbling practices soon, we risk blasting a hole in one layer of our armor and opening ourselves up as a nation to even more unnecessary sickness and death.
- This month, I spoke with five Americans about their pandemic pods. I reached out to them because they had talked in local media or on Twitter about their bubbles. Their strategies are by no means reflective of the entire country’s experience, but even within this small sample of middle-aged city dwellers and suburbanites, their behaviors were shockingly dissimilar. The deeper I probed, the more meaningless the terms pod and bubble seemed.
- Everyone was on more or less the same page as to the basics of the arrangement: Pod members interact with one another indoors without masks for extended periods of time, and do not do so with people outside the pod. But beyond that, they described practices that in some cases bore little resemblance to one another.
- Three of the bubbles I heard about are closed: No one on the inside has close contact with people on the outside, so with the exception of encounters in grocery stores and other public places, everyone knows exactly how many people they’re exposed to. John Skvasik, a 41-year-old librarian who lives in suburban Cleveland, is in a three-person pod with his 70-year-old mother and his uncle. (Skvasik spends 32 hours a week in the library, but he and his co-workers are all masked.) Stacy Selby, a 40-year-old who lives in Seattle and uses they/them pronouns, is in a 10-person bubble with the extended family of the children they nanny. Innosanto Nagara, a 50-year-old graphic designer and children’s-book author in Oakland, California, formed a “germ pod” of 16 with his wife and kids, his mother-in-law, and three other families who live on the same property.
- Other pods aren’t so self-contained. Jen Angel, a 45-year-old who lives in Oakland and owns a bakery (she was mixing vanilla-buttercream icing while we talked), has adopted a different strategy with her six housemates. Each of them is allowed to interact indoors and unmasked with a couple of their “most important people.” But there are no limits on the number of people those contacts see, or who those contacts’ contacts can mix with. Angel and her housemates meet weekly to go over the pod rules and map out everyone’s contacts and contacts’ contacts. As of last week, their most recent map included 35 people, and that didn’t include the unknown number of more distantly connected contacts.
- The podders I spoke with also had very different standards for rule-making and communication. Angel’s house, for example, has a Google Doc of agreements (“wash your hands as soon as you enter the house,” “immediately report exposures or symptoms to the rest of the pod”). Selby’s nannying contract includes a list of permitted activities. But some groups don’t have formal agreements at all. Sue Loh, a 44-year-old programmer and software developer who lives outside Seattle, told me that she considers her children’s nanny to be part of her household (she prefers household to pod or bubble because her family and her nanny are interacting for practical, not social, reasons). But Loh hasn’t asked her nanny or her nanny’s family to “limit their behavior at all,” she said, because “we just know from her own behavior that it’s probably not any more risk than we’re already taking.”
- By any strict definition, Loh’s and Angel’s groups are not bubbles at all, because they’re not closed networks. Open pods aren’t useless, especially if everyone is good about wearing masks, but they’re still riskier than a self-contained pod, no matter how pandemic-conscious members are in the rest of their life. “As soon as you sort of break your bubble, the connections can be infinite. And this is how [the virus] spreads,” McGraw, of Penn State’s Center for Infectious Disease Dynamics, said.
- The leakiness might be even more dangerous when bubble buddies don’t realize it’s a problem. “We get into trouble when people maybe think they’re in a pod, but some recommendation is being violated,” Meghan Moran, an associate professor of health, behavior, and society at Johns Hopkins, told me. That could lead to “a false sense of security,” further endangering people in the group. In other words, not only do some pods keep their members safer than others, but the very premise of safety can also put pod members at risk.
- Why, then, aren’t we all keeping our pods closed tight? Some variation in how Americans form their pods is unavoidable and even healthy. Local transmission rates, for example, can be used to inform best practices, and people in different living and work situations will come up with different solutions to the problem of how to socialize in a pandemic. But inconsistent or nonexistent messaging is undeniably playing a role in the confusion. For a concept that’s so important and widespread, health experts and the government have given remarkably little direct advice to the public.
- When I checked the CDC’s website for official resources on how to safely form a pandemic pod, I came up empty. (The agency did not respond when I asked whether such resources existed.) There are no guidelines to be found on the White House’s website or President-elect Joe Biden’s. Compare the treatment of the pod concept in the United States with that in New Zealand, where Prime Minister Jacinda Ardern used the word bubble in a briefing on March 24, and where the government’s coronavirus alert system clearly delineates what Kiwis should do with their bubbles at different restriction levels.
- The timing of Americans’ pivot to bubbles could also be a factor in our general confusion. When Ardern started talking about the strategy, New Zealand was preparing for winter in the Southern Hemisphere and needed to deal with the imminent threat posed by the indoors. But, as the experts I spoke with explained, in the U.S., the public-health guidance since the spring has generally shifted from an abstinence mindset of shunning the company of anyone you don’t live with to a focus on keeping your distance outdoors.
- Bubble and pod have also run into the same communication pitfalls as social distancing, quarantine, and a host of other new and reappropriated terms this year. Inventing new words or phrases is always a gamble: Their creators have relative control over their meaning, but the verbiage might not catch on. (When I asked UNC’s Robinson to think of a new, alternative phrase to replace pod, she thought for a moment before answering, “Closed behavioral network is not catchy. This is why academics are not good at making things up.”)
- Pod and bubble “resonate because they conjure up some kind of image for us,” Moran said, “which causes us to maybe assume we know what it means. But without that deeper level of understanding, different folks may be using the same term in very different ways, which can lead to misunderstandings.” Such mistaken assumptions are why Robinson prefers bubble to pod: She said that bubble evokes a more concrete image of a closed object with a defined inside and outside, whereas pod is more ambiguous.
- Under ideal circumstances, anyone trying to teach the American public a new health concept would follow a long, iterative process of creation, testing, and review. This is generally easier to do if you’re trying to address chronic health conditions, rather than a virus that is killing 1,500 people a day. But the coronavirus has presented public-health experts with the worst of both worlds: They need pandemic-fatigued Americans to adopt lasting behaviors for the remaining months until a vaccine can be distributed, but they can’t test their catchphrases as thoroughly as they’d like. This tension could explain some of the communication failures around bubbles: Messages that aren’t as carefully planned and tested as their creators would like have less of a chance of reaching—and inspiring helpful behaviors in—their audience.
- With winter fast approaching, Americans need pods now more than ever. But pods have also never been more dangerous. As with so many efforts to rein in the pandemic, a bubble strategy would be much easier to implement if viral spread were at least relatively under control. Instead, new cases and hospitalizations in the U.S. are higher than they’ve ever been, and deaths are also poised to break this spring’s horrifying records. According to Althoff, the Johns Hopkins epidemiologist, the higher transmission rates are, the more likely people are to get infected, and the higher the chances that the virus sneaks its way into any given pod.
- Still, podding has its benefits, even when implemented less than perfectly and in less than perfect environments. Forming a pod can be an impetus for having conversations about what constitutes acceptable C19 risk within a household or family. And those conversations can make the burden of navigating winter a bit lighter on everyone. “A hard thing about the pandemic is the feeling that you have to negotiate every interaction with someone, and that’s really exhausting mentally,” Robinson said. Talking about pod rules is a way to pre-negotiate, so that when you interact with people, you can focus more attention on the pleasure of their company.
- Talking about pods and bubbles might seem like more trouble than it’s worth, but it is, at the very least, a starting point for considering the consequences of our behaviors. As Robinson said, it’s “a chance to acknowledge that our dependence on each other has changed.” None of us should be shamed for relying on people we don’t live with, or for wanting to maintain our emotional health. We need one another. But we also need one another to exercise caution and restraint so that thousands more will not die in the name of preserving the nation’s social well-being.
K. Johns Hopkins COVID-19 Update
December 1, 2020
1. Cases & Trends
- From the first C19 case, it took 90 days for the global total to reach 1 million cases. From there:
- 1 million to 10 million- 86 days
- 10 to 20 million- 44 days
- 20 to 30 million- 37 days
- 30 to 40 million- 31 days
- 40 to 50 million- 21 days
- 50 to 60 million- 17 days
- From the first case reported in the US on January 22, it took 96 days to reach 1 million cases. From there:
- 1 to 2 million- 44 days
- 2 to 3 million- 27 days
- 3 to 4 million- 15 days
- 4 to 5 million- 17 days
- 5 to 6 million- 22 days
- 6 to 7 million- 25 days
- 7 to 8 million- 21 days
- 8 to 9 million- 14 days
- 9 to 10 million- 10 days
- 10 to 11 million- 7 days
- 11 to 12 million- 5 days
- 12 to 13 million- 7 days
- The US reported 12,999,624 cases on November 27, and it is likely that the US would have surpassed 13 million cases a day earlier, if not for delayed reporting over the Thanksgiving holiday.
- The US C19 average daily incidence and mortality both reached a peak over the Thanksgiving holiday weekend. On November 25, the US reported 173,518 new cases per day, a new record, and 1,658 deaths per day, the highest average since May 11. Both the daily incidence and mortality fell sharply since then, which is likely an artifact of reporting delays over the holiday weekend. Some of the direct effects of the Thanksgiving holiday are readily evident in the CDC’s C19 incidence reporting. As expected during a normal week, the daily incidence increased for data collected November 23-25, corresponding to Monday through Wednesday (the final workday before Thanksgiving, which falls on a Thursday). The reported incidence fell sharply on Thursday, November 26 (Thanksgiving Day); jumped back up on Friday, November 27; and then fell again for the weekend reports on November 28-29.
- It appears as though the national daily incidence may have passed an inflection point in mid-November. Prior to Thanksgiving, the daily incidence in a number of states—including Illinois, Iowa, North and South Dakota, and Wisconsin, all of which exhibited very high incidence during the current surge—began to taper off. However, with the interruptions to C19 reporting and the varying trends at the state level, it could be a little more difficult to anticipate daily incidence trends over the next week or so. Regardless of what the daily incidence trend looks like in the wake of Thanksgiving, C19 mortality in the US will likely continue to increase due to consistent and sharp increases in daily incidence over the past several weeks.
- It will be critical to monitor these trends over the coming weeks to determine the impact of Thanksgiving travel and gatherings. Any spikes in cases this week are likely attributable to disruptions in reporting over the holiday. It will likely take 2-3 weeks before we begin to see any actual effects from Thanksgiving in cases and hospitalizations and several weeks after that before we could observe early signs in terms of mortality.
- We have observed this timing following several other US holidays or major events in 2020, including Memorial Day (May 23-25) and Labor Day (September 5-7)/the return of students to college and university campuses (early September). If the US epidemic follows a similar timeline after Thanksgiving, we could potentially start to see increasing daily incidence in the US the week of Christmas and surging mortality early in 2021. With that in mind, however, reporting over the weeks of Christmas and New Year’s are also expected to be inconsistent, so the effect of the holiday season on the US epidemic may not be apparent until well into January.
- The Johns Hopkins CSSE dashboard reported 13.58 million US cases and 268,880 deaths as of 12:30pm EST on December 1.
2. US ISOLATION & QUARANTINE DURATION
- Last week, White House Coronavirus Task Force member ADM Brett Giroir commented that senior health officials are reevaluating the recommended time that individuals should quarantine after a known exposure to SARS-CoV-2 with an eye toward shortening the quarantine period. A recent study published in The Lancet found that the length of time that individuals can shed viable SARS-CoV-2 is shorter than previously believed. The US CDC currently recommends that exposed individuals quarantine for 2 weeks after their last close contact with a C19 case and that infected individuals should isolate for at least 10 days after the onset of symptoms and at least 24 hours after the fever resolves. Updated CDC guidance could potentially include a provision to shorten quarantine or isolation if accompanied by negative results for a diagnostic test administered after a certain amount of time. This story was initially covered by news media outlets this time last week; however, no formal announcement has been made regarding changes to the official CDC guidance.
- Reducing the quarantine or isolation period could potentially increase compliance by individuals who are not willing or able to isolate or quarantine for the full period currently recommended by the CDC. It could also reduce the impacts on employers and the US economy that result from workers being unavailable to perform in-person duties. There are concerns, however, that removing individuals from quarantine or isolation earlier could result in transmission by individuals who become or remain infectious after that point.
3. US LONG-TERM CARE FACILITIES
- As we have covered previously, residents of nursing homes and other long-term care facilities remain at high risk for severe C19 disease and death. A report published on November 25 by the Kaiser Family Foundation finds that more than 100,000 C19 deaths have been reported in the US among long-term care facility residents and staff. Notably, the cumulative total jumped from 84,136 in October to 100,033 in November, the highest 1-month increase since May. The report notes that these figures are likely an underestimate of C19 deaths at these facilities, including due to delays in reporting—and no reporting at all by Alaska. Long-term care facilities account for 40% of all US C19 deaths.
- The ongoing C19 surge in the Midwest region, and across most of the US, is fueling outbreaks in nursing homes and other long-term care facilities. In South Dakota, for example, the number of cases reported at these facilities tripled over the past month. Additionally, the total number of facilities reporting C19 cases is approximately 30% higher than previous peaks, with more than 1,300 facilities nationwide reporting cases in the first week of November alone. In one long-term care facility for military veterans in Illinois, 4 cases identified in early November grew to nearly 200 cases within 3 weeks, resulting in at least 28 deaths. Health officials and experts as well as representatives for long-term care facilities across the country continue to call on the federal government to provide additional funding and support to help these facilities prepare for, prevent, and respond to C19 outbreaks.
4. US VACCINE ALLOCATION
- As vaccine candidates get closer to receiving Emergency Use Authorizations (EUAs) under the US FDA, officials and health experts are working diligently to determine how the first doses should be allocated. Officials from the White House’s Operation Warp Speed announced that the initial doses purchased by the US government will be allocated to states based on population. From there, the current plan is for states to determine how best to allocate their allotted vaccines to individuals.
- Prioritizing the initial limited supply of vaccine doses is a major challenge, with a number of competing factors with respect to determining which individuals are the highest priority. Last week, the CDC’s Advisory Committee on Immunization Practices (ACIP), which issues recommendations for a variety of vaccines used in the US, presented its preliminary guidelines regarding “phased allocation” of SARS-CoV-2 vaccines. The preliminary guidance indicates that the highest priority (Phase 1a) should include frontline healthcare workers and residents in long-term care facilities. Phase 1b would expand access to other essential workers, including in the education, food and agriculture, public utility, law enforcement and corrections, emergency response (e.g., firefighters), and transportation sectors. And Phase 1c would include those at elevated risk for severe C19 disease, including those with underlying health conditions and those aged 65 and older. The Phase 1 plan received general agreement from the ACIP members, but additional data and discussion were needed.
- The CDC announced an emergency meeting of ACIP, held today from 2-5pm EST, with the aim of finalizing the initial allocation guidance. Considering that the US FDA’s Vaccines and Related Biological Products Advisory Committee is scheduled to meet on December 10 to discuss the EUA application for Pfizer’s candidate SARS-CoV-2 vaccine and that US states are supposed to submit vaccination plans this week, the CDC wants to finalize the allocation plans in order to mitigate any delays in initiating mass vaccination efforts. ACIP is expected to formally approve Phase 1a, but further analysis and discussion may be needed before developing and approving the guidance beyond that. The meeting is scheduled for 2-5pm EST today, and the proceedings will be streamed live.
- As a whole, Europe has passed the peak of its current C19 wave, and while a number of European countries have not yet turned the corner, some are beginning to announce plans to relax social distancing restrictions. The UK recently unveiled its C19 Winter Plan, which outlines steps to return England to a “regional, tiered approach” to C19 restrictions as opposed to a nationwide “stay at home” order. Retail stores, gyms and fitness centers, and other businesses will be permitted to reopen, and highly restrictive limits on attendance at religious services, weddings and funerals, and outdoor gatherings will be relaxed. The regional restrictions are scheduled to resume on December 2.
- The UK government also announced C19 policies specifically for the upcoming Christmas holiday, which will apply to all 4 countries in the UK—England, Northern Ireland, Scotland, and Wales. The Christmas plan “will allow some increased social contact for everyone,” including through the use of a “Christmas bubble.” The Christmas bubble can consist of individuals from up to 3 different households, and individuals in the bubble can gather in private homes, places or worship, and other locations without being limited by regional tiered restrictions. The Christmas bubble announcement comes at the end of a year in which holidays, ceremonies, and festivals across all religions have been muted by C19 restrictions.
- The relaxation of C19 gathering and travel restrictions specifically tied to Christmas, in the UK and other European countries, has generated frustration among some members of non-Christian religions, particularly those who faced restrictions earlier in the year during their own religious holidays. There is also concern that the temporary relaxation of C19 restrictions that would permit increased travel and larger gatherings could result in another surge early in 2021. European governments are attempting to balance C19 health risks against religious practices, social gatherings, and broad economic impact associated with Christmas.
- France is also scaling back its C19 restrictions. On November 24, French President Emmanuel Macron announced a timeline and epidemiological metrics for easing some social distancing restrictions over the coming weeks. Beginning on November 28, France eased travel restrictions and permitted outdoor activities to resume and some retail businesses and home services to reopen.
- If France is able to reduce daily incidence to fewer than 5,000 new cases per day and intensive care hospitalizations to fewer than 3,000 patients, it could enter the next phase, which will further reduce travel restrictions; allow theaters, cinemas, and museums to reopen; and permit indoor recreational activities. And if the epidemiological conditions are satisfactory on January 20 (not specified explicitly), restaurants and indoor sports facilities can reopen and high school students can resume in-person classes.
- While some European countries are beginning to remove restrictions, others are extending current C19 measures. For example, Greece is reportedly extending its current “lockdown” period by a week, through December 7, following a record high 121 deaths on November 28. Greece’s daily C19 incidence peaked in mid-November, but the government has been fairly aggressive in terms of implementing C19 restrictions.
- One of Greece’s principal concerns is that long-term economic struggles have negatively impacted national health system capacity, and implementing restrictions earlier and longer than other European countries could curb transmission before hospitals are overwhelmed. The current lockdown began in early November, with highly restrictive measures, including a requirement for individuals to notify the government via text/SMS message before leaving their homes. Reportedly, Greece recently issued more than €500,000 in fines and ordered a 15-day closure of multiple businesses in a single day following violations of national C19 restrictions.
6. ASTRAZENECA VACCINE TRIAL DATA
- Following the release of interim Phase 3 clinical trial data for its candidate SARS-CoV-2 vaccine, AstraZeneca and the University of Oxford (UK) are facing criticism regarding the circumstances surrounding findings that indicated 90% efficacy in participants who received a half-dose in the first of their 2 injections, which was considerably higher than in participants who received 2 full doses. Beyond the unexpected results—i.e., higher efficacy among participants receiving smaller doses—the fact that the researchers inadvertently administered the wrong dose to a portion of the study group raised serious concerns, particularly because this was omitted from the press release announcing the interim results.
- A number of factors could be influencing the higher efficacy reported among the subset of participants who received the initial half-dose, and further investigation is needed. Perhaps most notably, the participants who received the half-dose were reportedly all aged 55 years and younger, who would be at lower risk for severe disease and death than older individuals (e.g., age 65 years and older). Experts from around the world, including at the University of Oxford and the WHO, have called on AstraZeneca to publish more detailed trial data. Reportedly, AstraZeneca aims to publish the full data and analysis in a peer-reviewed journal “within the next week or so.” A senior executive for AstraZeneca dismissed concerns about the accidental half-dose and emphasized that the overall 70% efficacy still exceeds the minimum threshold of 50% set by multiple national-level regulatory agencies. While 70% would be sufficient for a novel SARS-CoV-2 vaccine, it is still below the 90-95% reported by Pfizer and Moderna.
7. MODERNA VACCINE EUA APPLICATION
- Moderna Therapeutics announced that the Phase 3 clinical trials for its candidate SARS-CoV-2 vaccine reached the primary efficacy endpoints. In total, the trials detected 196 cases of C19 among 30,000 total participants, including 185 cases among the placebo group. This corresponds to an overall efficacy of 94.1%, nearly identical to the 94.5% efficacy based on preliminary Phase 3 trial data announced on November 16. The most recent press release also indicates that the vaccine demonstrated similar efficacy across all “age, race and ethnicity, and gender demographics.” Additionally, Moderna reported that all 30 severe cases of C19, including 1 death, were among participants in the placebo group, demonstrating that the vaccine is capable of substantially mitigating risk of severe C19 disease.
- Yesterday, Moderna submitted requests for Emergency Use Authorization to the US FDA and Conditional Marketing Authorization to the European Medicines Agency. Moderna expects the US CDC’s Vaccines and Related Biological Products Advisory Committee to meet to review its vaccine clinical trial data on December 17, one week after the committee meets to review the Pfizer vaccine.
- If the vaccine receives an EUA, Moderna’s CEO, Stéphane Bancel, indicated that vaccinations could begin as early as December 21. Evaluation of the vaccine is already underway in multiple other countries, including Canada, Israel, Singapore, Switzerland, and the UK. While limited data are presented in the press release, Moderna committed to publish more detailed data and analysis in a peer-reviewed publication.
- In addition to the clinical trial data, Moderna announced that it finalized an agreement to provide an additional 2 million doses of the vaccine to the UK government, bringing the UK’s purchase from Moderna to 7 million total doses.
8. UK VACCINE AUTHORIZATION
- The UK is on track to be the first country to authorize the Pfizer C19 vaccine for use among its citizens. The UK’s Medicines and Healthcare Products Regulatory Agency is currently conducting an expedited review of Pfizer’s vaccine candidate, under a special government rule to bypass certain EU regulatory processes. Sources indicate that the authorization could be announced as early as December 7, with distribution beginning that same day.
- It has been reported that British hospitals were told on Sunday to prepare for vaccine rollout within the next 10 days. The UK has ordered 40 million doses of the Pfizer vaccine, which corresponds to 20 million individuals at 2 doses per person. According to a report from the UK’s Joint Committee on Vaccination and Immunisation, long-term care facility and nursing home residents and associated healthcare workers are the first priority group for vaccination, with adults aged 80 years and older and NHS healthcare workers following in the next tier.
- While the Pfizer vaccine would be the first to be distributed in the UK, it is unlikely to be the only candidate that will eventually be used in the country. The UK has invested in 7 different vaccine candidates from various companies, with the majority of the UK’s investment going to vaccine developed by UK-based AstraZeneca and the University of Oxford. Out of a total of 350 million doses purchased across all seven candidates, 100 million of those doses are expected to come from AstraZeneca. The UK government directed MHRA last week to begin evaluating the AstraZeneca data for safety, quality, and efficacy. If authorized for use, this vaccine could be rolled-out not long after the Pfizer product.
9. NORTH KOREA
- While North Korea has yet to officially report a single case of C19, intelligence sources suggest that government officials are taking extreme measures against the pandemic. It is difficult to understand exactly what the North Korean approach is to C19, but recent intelligence updates can provide some insight. While North Korea typically maintains highly restrictive limitations on international travel, travel to and from the country has stopped almost completely. Additionally, North Korea is believed to have drastically decreased trade with China, its only major trading partner, likely in an effort to prevent C19 from entering the country. China accounts for at least 90% of all trade with North Korea, so the reduction in imports and exports will have significant impacts on the North Korean economy and the North Korean people. In addition to stricter border controls, sources believe that large-scale lockdowns have also been put into place.
- The travel sector, particularly the airline industry, has been among the hardest hit during the C19 pandemic, largely due to a combination of travel restrictions and traveler concerns about exposures in other countries or during travel. Air travel has steadily started to increase compared to earlier in 2020, and many airlines have made major changes to their normal operations and requirements for passengers, including enhanced cleaning and hygiene practices, increased physical distancing, and mask mandates. Now, more airlines are considering testing requirements and, with potential vaccines on the horizon, vaccination requirements for passengers.
- Delta Airlines recently announced a “COVID-free” route from Atlanta to Rome that would require passengers to take 3 separate tests: 2 leading up to departure and 1 upon arrival. The first test would be a PCR-based test taken no later than 72 hours before departure. The second test would be a rapid antigen test at the gate before boarding. A third test, also a rapid antigen test, would be administered upon landing in Rome and before clearing through customs. Travelers will also be required to undergo another rapid antigen test prior to boarding their return flight to the US. Epidemiological models, developed in conjunction with experts at the Mayo Clinic (Minnesota, US), estimate that the new protocols will significantly decrease transmission risk on Delta’s flights, potentially as low as “one in a million.”
- With the prospect of a SARS-CoV-2 vaccine in the near future, some airlines are considering mandating vaccination for travelers. The CEO of Australia-based airline Qantas stated that customers will be required to provide proof of vaccination before taking international flights. He also indicated medical issues “should be the only basis” for exemptions to the vaccination policy, which suggests that personal belief or religious exemptions may not be accepted by the airline.
- The International Air Transport Association (IATA) is preparing for these types of mandates by developing its IATA Travel Pass smartphone application, which will allow travelers to input and present their vaccination and testing information to relevant travel authorities. The application will be free for travelers and will include information on their destination’s travel restrictions and requirements and will provide digital security for personal medical information related to C19.