Recent Developments & Information
June 26, 2020
Reliable information is the best tool available to protect your family from the pandemic and its shockwaves
“The virus is not going to disappear.”Dr. Anthony Fauci
“I am very cautious and I don’t — still don’t sleep well at night because we have a long way to go.”Admiral Brett P. Giroir, assistant secretary for public health
“Michael Osterholm, an infectious disease epidemiologist at the University of Minnesota, looked at eight influenza epidemics since the mid-1700s. In each case the virus faded only to come back in a much more lethal wave.”Donald G. McNeil Jr., science and health report for the NY Times
A. The Pandemic As Seen Through Headlines
B. Numbers & Trends
C. The Impact of Rapidly Increasing New US Cases
- Latest State-Level Coronavirus Tracker Shows Alarming Trend Reversal
- New C19 Cases Soar, But New Deaths Decline As Younger Patients Recover
- Getting realistic about the coronavirus death rate
- Study confirms the key symptoms to look out for in cases of C19
- CDC adds 3 new coronavirus symptoms to list
- Pink Eye Identified as Possible Primary Symptom of C19
E. New Scientific Findings & Research
- Statin use is linked to lower death rate in hospitalized C19 patients
- MIT Researchers Design Experimental Peptide That Targets and Destroys C19
- Study is first to identify potential therapeutic targets for C19
- Early childhood vaccinations might protect children from C19
- Scientists Warn About Transmission or Coronavirus to Animals and then Back to People
- Rise of the Biohackers: Do It Yourself Vaccine (!)
- Sanofi, a straggler in the C19 vaccine race, accelerates its plans
- The Race for a Vaccine: Will Collaboration Trump the Desire to Win?
G. Concerns & Unknowns
- CDC broadens guidance on Americans facing risk of severe C19 [Recommended]
- The coronavirus is leaving some people with permanent lung damage
- Mounting clues suggest the coronavirus might trigger diabetes
- Study Raises Concerns for Pregnant Women With the Coronavirus
- Preventing dangerous blood clots from C19 is proving tricky
- CDC says C19 cases in U.S. may be 10 times higher than reported
- What antibody tests tell us about C19
I. The Road Back?
J. Projections & Our (Possible) Future
K. Practical Tips & Other Useful Information
L. Links to Other Scientific Findings & Research
A. The Pandemic As Seen Through Headlines
(In no particular order)
- New COVID-19 Cases Soar, But New Deaths Decline As Younger Patients Recover
- With COVID-19 Cases Rising, Some States Slow Their Reopening Plans
- Houston ICU Capacity Reached, City Activates COVID-19 Overflow
- Texas Gov. Abbott pauses reopening amid coronavirus surge
- New Jersey’s coronavirus death toll adds nearly 2,000 probable fatalities
- Futures Accelerate Slide On “Second Wave” Fears Ahead Of Jobless Claims
- Canned Meat Booms As COVID-Recession Crushes Consumers
- “Depression-Like Crisis” Unfolding With No V-Shaped Recovery Until 2023, UCLA Anderson Warns
- U.S. Economy on the Road to Recovery With Second Wave Looming
- US economy shrank 5% in first quarter, more bad news ahead
- “All About Damage Control” – As Spain Lifts Lockdown, The Crisis Begins For Tourism Industry
- Scientists test if gargling salt water helps treat coronavirus
- ‘Don’t be a sheep’: Washington sheriff urges residents to defy mask order
- Florida residents furious over ‘devil’s law’ requiring face masks
- Secret Service agents quarantine after Tulsa Trump rally
- Dogs are joining the fight against NYC’s coronavirus rat problem
- An app for football fans became a digital contact tracing tool — and could be a litmus test for Covid-19 technology
- Democrats Tell Convention Delegates to Stay Home During Pandemic
- Covid Antibody Tests Not Ready for U.K. Roll-Out, Experts Warn
- France Outlines Virus Furloughs That Could Run for Two Years
- Swedish Expert Who Doubted Face Masks Reconsiders Their Use
- Fear of Vial Shortage for Covid Vaccines Prompts Flurry of Deals
- The Pandemic’s Worst-Case Scenario Is Unfolding in Brazil
- ‘Smart Lockdowns’ Are the Future in Europe
- The number of Americans who have been infected is most likely 10 times higher than the 2.3 million reported cases
- NYC is on track to enter Phase 3 of the state’s reopening plan on July 6, which would allow indoor dining and personal-care services to resume
- In South Korea, citizens are advised to carry two types of masks — a surgical mask for normal use, and a heavy-duty mask for crowded situations
- The Kentucky Derby, planned for Sept. 5, will allow spectators to watch the race in person, track officials announced today
- Mexico Nearly Surpasses Iran for Coronavirus Cases
- NY Gov. Cuomo to FL Gov. DeSantis: ‘You Played Politics with This Virus and You Lost’
- NFL Cancels Cowboys, Steelers Hall of Fame Game Due to Coronavirus
- British soccer team apologizes after Osama Bin Laden cutout appears in crowd
- Connecticut officials unveil plans to reopen schools in fall
- Face coverings are now mandatory at Las Vegas casinos
- Coronavirus-tracking apps might be full of ransomware, report warns
- Florida’s new coronavirus cases soar for second straight day
- Surprise! Family party leads to coronavirus infections
- Entire college basketball team quarantined because of coronavirus
- Uruguay and Paraguay achieve near-total victory over coronavirus
- ‘Don’t be dumb like me:’ Another WWE announcer says she’s gotten coronavirus twice
- Europe sees ‘significant resurgence’ of coronavirus after lockdowns lifted
- 52 first dates: With lockdown lifted, this woman tried to make up for lost time
- Ill-advised spring break trip to Mexico led to coronavirus outbreak among 60 students
- US coronavirus deaths forecast to hit 180,000 by October
- Over 600,000 re-enter ‘soft lockdown’ in Germany after meat plant outbreak
- Large-scale coronavirus vaccine trial begins in South Africa
- India, with nearly 500,000 cases, aims to test all 29 million people in New Delhi
- Russian hackers target Americans working at home
- Another pause for Hollywood’s plans
- In Paris, the Eiffel Tower partially reopened today, and the Louvre plans to welcome visitors again starting July 6
- After several recent local outbreaks, Germany’s infection rate has dropped, a sign that infections could start decreasing again
- Infected pregnant women wind up in hospitals and ICUs at higher rates
- China has warned its citizens in Russia to stop falsifying virus test results that they are required to provide when boarding flights home
- A study of the Austrian ski resort village of Ischgl found that 42% of residents had coronavirus antibodies — the highest infection rate recorded so far
- Coronavirus stimulus checks went to 1.1 million dead people, agency says
- How the split over face masks sums up America’s chaotic coronavirus response
- Hospitals see shortages of a cheap steroid that one study says helps Covid-19 patients
- California’s Disneyland Puts Reopening on an Indefinite Hold
- The nation’s coin supply is coming up short as lockdowns keep people from emptying their coin jars for paper bills
- Everything is fine and normal. Just ask the mannequin at the next table.
B. Numbers & Trends
Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the preceding day. Green highlights indicate a decrease or no change and yellow highlights indicate an increase.
1. Cases & Tests
- Total Cases = 9,702,189 (+1.9%)
- New Cases = 181,990 (+7,360)
- Growth Rate of New Cases (7 day average) = 3.8% (+1.1%)
- New Cases (7 day average) = 161,743 (+5,980)
- Highest number of new cases since beginning of pandemic
- Highest 7 day average of new cases since beginning of pandemic
- Growth rate of new cases is accelerating
- More than one million cases are being reported each week
US Cases & Testing:
- Total Cases = 2,504,588 (+1.6%)
- New Cases = 40,184 (+1,794)
- Percentage of New Global Cases = 22.1% (-0.3%)
- Growth Rate of New Cases (7 day average) = 4.4% (-1.1%)
- New Cases (7 day average) = 34,120 (+1,452)
- Total Number of Tests = 30,732,552 (+672,688)
- Percentage of positive tests (7 day average) = 6.0% (+0%)
- Highest number of new cases since beginning of pandemic
- Highest 7 day average of new cases since begging of pandemic
- Growth rate of new cases is accelerating
- Total Deaths = 490,988 (+1.5%)
- New Deaths = 5,178 (+102)
- Growth Rate of New Deaths (7 day average) = (-5.0%)
- New Deaths (7 day average) = 4,637 (-246)
- During the last month, the 7 day average has been fluctuating between 4,091 (5/26) and 4,823 (6/22)
- Although the 7 day average had decreased by 246, the 3 day average has increased from 3,885 to 5,241, an increase of 34.9%
- It is too early to determine if recent increase in new deaths is normal variability or the beginning of an upward trend
- Total Deaths = 126,780 (+0.5%)
- New Deaths = 649 (-163)
- Percentage of Global New Deaths = 12.5%
- Growth Rate of New Deaths (7 day average) = -31.1%
- New Deaths (7 day average) = 609 (-275)
- Lowest 7 day average of new deaths since March 31 (606)
- Substantial drop in 7 day average growth rate of new deaths
- 3 day average of new deaths increased from 404 to 776 over the last 4 days, an increase of 92.1%
- Too early to tell if increase during the last 4 days is normal variability or the beginning of an upward trend
C. The Impact of Rapidly Increasing New US Cases
1. Latest State-Level Coronavirus Tracker Shows Alarming Trend Reversal
- According to the latest Goldman Sachs state-level coronavirus tracker, the prevalence of coronavirus symptoms is rising, with the share of patients seeking care with symptoms of Covid-like illness at 3.5%, up 0.4% from 2 weeks ago.
- Daily confirmed new cases have steadily been increasing during the past several weeks. A big part of this is due to increased testing: indeed, the volume of daily coronavirus tests has risen 23% over the last two weeks, while the positive test rate has risen by 1.3% to 6.2%. On the flipside, fatalities have declined over the last two weeks (-12%), although fatalities lag new cases by multiple weeks.
- As a reminder, the federal government recommends states meet four criteria to proceed with reopening:
- symptoms should be declining,
- new cases should be declining,
- the positive test rate should be below 10%,
- at least 30% of ICU capacity should be available.
- Currently Arizona and South Carolina—accounting for 4% of the US population—meet none of the four criteria; 8 states including Texas and Florida meet only 1 criterion; 14 meet 2; 12 meet 3; and only 14 states meet all 4 criteria.
- As Goldman notes next, while states make their own decisions about reopening, a decline in hospital capacity below 20% could pressure states to consider slowing or reversing reopening. In this context, according to the latest CDC data, Alabama and Maryland currently have 23% of ICU beds available (with Covid patients accounting for 7% and 13% of occupancy respectively), and Arizona has 25% available (with Covid patients accounting for 11%).
- Looking at the average US state, Goldman concludes that it currently meets 2 of the 4 federal gating criteria, with the most notable recent development being that the prevalence of Covid-like illness symptoms is declining in states representing 20% of the population, compared to close to 50% a week ago. New cases are declining in states representing only 30% of the population, also worse than last week.
- More encouragingly, the vast majority of states have a positive coronavirus test rate below 10%, and states covering 80% of the population have available ICU capacity above 30%.
- The key questions: is the above trend reversal sufficient to gut the recovery narrative and force states to resume hated shutdowns in the coming weeks? And if so, how will the Trump administration react and will the population even follow any new lockdown measures?
2. New C19 Cases Soar, But New Deaths Decline As Younger Patients Recover
Some public health policy experts fear spreading unfounded alarm about rising infection rates risks deep harm to Americans’ livelihoods and mental health due to prolonged, widespread shutdown
- Even though new coronavirus infections are rising in America and around the world, new coronavirus deaths are largely flat, a trend largely missing from most mainstream media coverage.
- Experts say the fact that new coronavirus deaths appear to remain flat is driven by more younger patients getting infected and recovering amid reopenings as the worst of the pandemic passes.
- On Wednesday evening, the Washington Post issued a breaking news email alert headlined “New coronavirus cases in the U.S. soar to highest single-day total.”
- “Across the United States,” reported the Post, “more than 36,000 new infections were reported by state health departments on Wednesday — surpassing the previous single-day record of 34,203 set on April 25.”
- Yet the article failed to mention that even while new infections are on the rise, new C19 deaths are not.
- This vital information gap in the media is causing some health policy experts to worry that fear about the coronavirus — evidenced, for example, by Wednesday’s sharp stock market drop — is not founded in facts, particularly about how the virus disparately impacts different age groups.
- The spreading of unfounded alarm, the experts fear, could risk deep harm to Americans’ livelihoods and mental health due to a prolonged, widespread shutdown.
- The coronavirus has ravaged elderly populations in nursing homes and those with underlying comorbidities, but now the virus appears to be striking those who are younger and healthier and more able to withstand the disease and return to life normally.
- Vanderbilt University School of Medicine professor Dr. William Schaffner, who specializes in preventive medicine and infectious diseases, noted in an interview with Just the News that for example, in Florida, reports indicate that it is middle-aged and younger adults now being hit with C19.
- Data from Oxford University show that even though the confirmed daily reported C19 cases have been ticking up in the United States in recent days, daily confirmed deaths have not risen. Similar trends are seen worldwide, according to Oxford: Daily confirmed cases have been rising, but daily confirmed deaths have not.
- “The data has made it clear that the impact of C19 on those in long-term care facilities or older adults with underlying conditions has been devastating, and more cautious policies are suggested,” Joshua Archambault, a senior fellow in healthcare policy at the Foundation for Government Accountability, told Just the News. “But for younger adults, if local hospital capacity is not an issue, then more open policies can be recommended, as long as they are paired with the common-sense best practices that most know to follow already.”
- Archambault recommended that to find a sustainable “new normal” leaders should analyze data daily or weekly to update any advice to citizens, instead of blanket recommendations or mandates for citizens based on older data.
- “Without nuance, individuals’ economic lives are ruined, and the negative impacts of isolation can set in, leading to more domestic violence, and suicide,” Archambault said.
- “There are two sides to pandemic shutdowns. This will mean different recommendations for different groups and will reflect local concerns related to hospital capacity. That is why looking at just one data source is not enough. Leaders should be looking at running averages for hospital admission rates, mortality rates, and infection rates by different groups to make recommendations.”
3. Getting realistic about the coronavirus death rate
- With coronavirus infections rising again across the nation, the question of just how lethal the virus is has become more crucial than ever.
- Early in the epidemic, public-health experts feared the virus might kill up to 2% of those infected, potentially causing millions of deaths in the United States and tens of millions worldwide.
- Those terrifying estimates prompted the lockdowns that have done incalculable harm to the economy, shattered small businesses and left children traumatized and untold numbers suffering from brutal isolation.
- But we now know much more about the virus. And we know its lethality is lower than we originally feared — and highly concentrated in the very elderly and people with serious health problems.
- In fact, the CDC estimated in May that the coronavirus kills about 0.26% of the people it infects, about 1 in 400 people.
- New estimates from Sweden suggest that only 1 in 10,000 people under 50 will die from the virus, compared to 1 in 14 of people over 80 and 1 in 6 of those over 90.
- Estimates for the coronavirus’ lethality have fallen so sharply because calculating the so-called infection fatality rate requires scientists and physicians to know both the total number of deaths and the total number of people infected.
- Tracking deaths is relatively easy. But tracking infections can be tough. Many people who are infected with respiratory viruses like influenza or the novel coronavirus have only mild symptoms or none. They may never be tested or even know they are infected.
- Thus, in the early stages of an epidemic, scientists must guess at the number of mild and hidden infections.
- Probably the best way to discover the real number is through antibody tests, which measure how many people have already been infected and recovered — even if they never had symptoms.
- Unlike some other countries, the United States still hasn’t completed a national random antibody study — yet another way in which our public-health establishment has failed to get the data we need to make good decisions about lockdowns. But some counties, states and countries have.
- Those studies consistently show that far more people have been infected with and recovered from the coronavirus than suggested by data from tests that only measure current infections. Tests of municipal sewage systems — measuring the virus’ genetic signature in wastewater — have had similar findings.
- Nearly all the studies find between 10 and 100 times the number of total infections as reported infections, with the average somewhere around 20 to 25 times.
- In other words, while the CDC reports 2.34 million Americans have been infected with the coronavirus, the actual number of infected and recovered people may be closer to 50 million. (CDC Director Robert Redfield told journalists Thursday that the number of cases may be 10 times higher than the earlier 2.34 million.)
- Thus, the death rate, which would be 5.2 percent based on that 2.34 million figure, is actually more like one-20th as high — or 0.26 percent.
- To be sure, these estimates still have some uncertainty. The actual figure could be as low as 0.1 percent or as high as 0.4 to 0.5 percent, though treatment advances should mean it will trend lower over time. Even at 0.26 percent, the rate is still significantly higher than influenza most years, more comparable to a bad flu strain like the 1968 Hong Kong flu.
- But it is far lower than we initially thought — a fact that should be cause for celebration.
- Instead, some media outlets insist on using the out-of-date estimates that are much higher. For example, an ESPN article this week said public discussions about reopening the National Football League were “ignoring a mortality rate that has been estimated at 1.4 percent.” That figure is more than five times the CDC’s best estimate. Even more jarring, it is more than 100 times the actual risk to people in their 20s and 30s — the age range for nearly all NFL players.
- Using those overstated estimates is a recipe for panic, bad public policy — and continued lockdowns that may delay to return to normality.
- Let’s hope that isn’t the reason people in the media are using them.
1. Study confirms the key symptoms to look out for in cases of C19
- A new large-scale review has confirmed some of the major symptoms associated with C19, including a persistent cough, fever and loss of smell.
- Carried out by researchers from the University of Leeds, UK along with four other universities, the new review is one of the biggest so far to investigate C19 symptoms and included data from 148 separate studies.
- In total, the researchers had access to data on 24,410 adult cases of C19 in nine countries, including the UK, China and the USA, which enabled them to identify the common symptoms of the virus.
- The findings, published in the online journal PLoS ONE, showed that the most common symptom of the virus was fever, which was found in 78% of C19 cases. However, the researchers also found that the rates of this symptom varied from country to country, with 72% of patients in Singapore reporting a fever, compared to just 32% of patients in Korea. The second most common symptom was a cough, found in 57% of patients, but again, the number of patients who reported this symptom varied in each country, from 76% in the Netherlands compared to 18% in Korea. The researchers say that these variations could be due to the way data was collected.
- Other common symptoms included fatigue (31% of cases), a loss of smell (25%) and difficulty breathing (23%).
- The researchers also found that from the patients who required hospital treatment, 19% were in the intensive care unit, 17% needed non-invasive help with their breathing, nine percent needed invasive ventilation and two percent needed an artificial lung. The mortality rate was seven percent.
- They say that the findings confirm the list of symptoms given by the World Health Organization at the start of the pandemic. However, they also add that it’s likely that a large proportion of people who had the virus did not display symptoms.
- Ryckie Wade, a surgeon and Clinical Research Fellow at the Leeds Institute of Medical Research who supervised the research commented on the findings saying, “This analysis confirms that a cough and fever were the most common symptoms in people who tested positive with C19.”
- “This is important because it ensures that people who are symptomatic can be quarantined, so they are not infecting others.
- “The study gives confidence to the fact that we have been right in identifying the main symptoms and it can help determine who should get tested.”
2. CDC adds 3 new coronavirus symptoms to list
- The CDC appears to have recently added three new symptoms of the novel coronavirus to its ongoing list.
- Congestion or runny nose, nausea, and diarrhea were added, joining the federal agency’s list that already included fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell and sore throat.
- “This list does not include all possible symptoms. CDC will continue to update this list as we learn more about C19,” per the CDC.
- The new symptoms were quietly added, with one news outlet reporting that the changes were made on May 13.
- The CDC made a similar change in April when officials added six additional symptoms to the list. At the time, these new changes included chills, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell.
- When the pandemic first began, fever, cough, and shortness of breath were reported to be the most common signs of a C19 infection.
- Symptoms can range from mild to severe, with most people beginning to experience them two to 14 days following exposure to the coronavirus.
3. Pink Eye Identified as Possible Primary Symptom of C19
- A case of pink eye is now the reason to be tested for C19, according to University of Alberta researchers.
- Coughing, fever and difficulty breathing are common symptoms of the illness, but a recent case study involving an Edmonton woman and published in the Canadian Journal of Ophthalmology has determined that conjunctivitis and keratoconjunctivitis can also be primary symptoms.
- In March, a 29-year-old woman arrived at the Royal Alexandra Hospital’s Eye Institute of Alberta with a severe case of conjunctivitis and minimal respiratory symptoms. After the patient had undergone several days of treatment with little improvement—and after it had been determined that the woman had recently returned home from Asia—a resident ordered a C19 test. The test came back positive.
- “What is interesting in this case, and perhaps very different to how it had been recognized at that specific time, was that the main presentation of the illness was not a respiratory symptom. It was the eye,” said Carlos Solarte, an assistant professor of ophthalmology at the U of A.
- “There was no fever and no cough, so we weren’t led to suspect C19 at the beginning. We didn’t know it could present primarily with the eye and not with the lungs.”
- According to Solarte, academic studies at the outset of the pandemic identified conjunctivitis as a secondary symptom in about 10 to 15% of C19 cases. Since then, scientists have gained greater knowledge of how the virus can transmit through and affect the body’s mucous membrane system, of which the conjunctiva—the clear, thin membrane that covers the front surface of the eye—is an extension. Conjunctivitis and keratoconjunctivitis are now recognized by Alberta Health Services as possible primary symptoms of C19.
- While the finding provides important new health information for the public, it also makes eye exams more complicated for ophthalmologists and staff.
- “The patient in this case eventually recovered well without any issues. But several of the residents and staff who were in close contact with the patient had to be under quarantine,” said Solarte. “Fortunately, none who were involved in her care also tested positive.”
- Patients coming into an eye clinic with conjunctivitis and keratoconjunctivitis are now treated as potential cases of C19 and extra precautions are taken by staff. Workers performing an eye exam are strongly advised to wear personal protective equipment to minimize potential exposure to the illness.
- “It’s important to ensure that everyone is well protected. Our residents are now using gloves, gowns and facial masks every time they see one of these patients,” said Solarte. “We need to be really careful about protective measures to examine these patients.”
E. New Scientific Findings & Research
1. Statin use is linked to lower death rate in hospitalized C19 patients
- The use of cholesterol-lowering drugs called statins is associated with a lower death rate and a lower incidence of mechanical ventilation in patients hospitalized with C19, researchers report June 24 in Cell Metabolism. The large-scale retrospective study also showed that mortality risk and other negative outcomes were not increased by combination therapy consisting of statins and blood pressure-lowering drugs called angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).
- “These results support the safety and potential benefits of statin therapy in hospitalized patients with C19 and provide a rationale for prospective studies to determine whether statins confer protection against C19-associated mortality,” says senior study author Hongliang Li of Wuhan University. “Moreover, our findings represent an important contribution to the accumulating clinical evidence regarding the beneficial or detrimental effects of prescribing ACE inhibitors or ARBs to patients with C19.”
- Currently, there is no vaccine or specific antiviral drug approved to prevent or treat C19. Because a vaccine or drugs for C19 will likely not be available for months or even years, repurposing clinically approved therapies might be a more attractive option. Statins may serve such a purpose because these drugs slow the progression of lung injury in animals, improve immune cell responses, and strongly reduce inflammation, which is likely responsible for severe C19 complications such as organ damage.
- Although statins generally have an excellent safety profile in humans, animal studies have shown that they increase the expression of angiotensin-converting enzyme II (ACE2)–the receptor that SARS-CoV-2 binds to and uses to enter host cells. On the other hand, animal studies have also shown that ACE2 protects organs such as the lungs against virus-induced injury. As a result, it has not been clear how clinical outcomes in patients with C19 are affected by the use of statins, either alone or in combination with ACE inhibitors and ARBs, which are commonly prescribed with statins and also increase ACE2 expression in animals.
- To address this gap in knowledge, Li and his collaborators carried out a retrospective study of 13,981 C19 patients admitted to 21 hospitals in Hubei Province, China. Among these patients, 1,219 used statins, primarily atorvastatin at an average dose of 20 mg/day. Among patients with hypertension (i.e., high blood pressure), 319 used statins combined with ACE inhibitors or ARBs, and 603 used statins combined with other antihypertensive drugs.
- The researchers analyzed mortality rates and secondary outcomes, including the incidence of invasive mechanical ventilation, admission to intensive care units, acute respiratory distress syndrome, and liver, kidney, or heart injury. Because patients on statins were older and had a higher incidence of lung lesions and chronic diseases, the researchers also performed analyses on subsets of patients that were matched for baseline characteristics such as age, disease severity, and pre-existing conditions.
- Over a 28-day follow-up period, statin use was associated with a lower death rate and a lower incidence of mechanical ventilation. Statin use was associated with 5.5% mortality rate, compared to 6.8% without statin use, representing a 19% decrease. When the researchers examined the matched cohort of 861 patients in the statin group and 3,444 patients in the non-statin group, statin use was associated with a 45% decrease in the mortality rate, from 9.4% to 5.2%. In the matched cases, statin use was also associated with lower levels of three inflammation biomarkers, and a lower incidence of acute respiratory distress syndrome and admission to intensive care units.
- In the unmatched sample, mortality and secondary outcomes over 28 days were not affected by the use of statins combined with ACE inhibitors or ARBs, compared to combination therapy consisting of statins and other antihypertensive drugs. But in the matched cohort with 204 patients in each group, the use of statins combined with ACE inhibitors or ARBs versus other antihypertensive drugs was associated with a 65% drop in the death rate (3.4% versus 9.8%) and a lower incidence of heart injury and acute respiratory distress syndrome.
- “Although the use of an ACE inhibitor or ARB was once speculated to be potentially harmful in patients with C19, several professional societies have recommended the continued use of these drugs in patients with C19 and pre-existing hypertension,” Li says. “To our knowledge, the results from this study are the first clinical evidence supporting the notion that the risk of C19 mortality is not increased by using ACE inhibitors or ARBs in combination with statin treatment.”
- However, the study does not prove that the lower death rate of patients with C19 is directly caused by the use of statins, either alone or in combination with ACE inhibitors or ARBs. For now, it is also unclear whether the findings apply to non-hospitalized patients with C19. Moreover, the results of retrospective studies should be interpreted with caution, Li says. “Although these data do provide supportive evidence for the safety of statins or the combination of statins with ACE inhibitors or ARBs for treatment in patients with C19, further randomized controlled trials to prospectively explore the efficacy of statins on C19 outcomes appear justified.”
2. MIT Researchers Design Experimental Peptide That Targets and Destroys C19
Computational modeling yields a protein fragment that could bind to coronavirus spike proteins and destroy them.
- Using computational models of protein interactions, researchers at the MIT Media Lab and Center for Bits and Atoms have designed a peptide that can bind to coronavirus proteins and shuttle them into a cellular pathway that breaks them down.
- This type of peptide could hold potential as a treatment that would prevent the coronavirus from reproducing itself within infected cells, the researchers say.
- “Our idea was to use computational techniques to engineer a peptide that could be a therapeutic for C19. Once the peptide gets in the cell, it can simply tag and degrade the virus,” says Pranam Chatterjee, a recent MIT PhD recipient and the lead author of the study.
- The researchers have tested the peptide in human cells, and they are now planning additional cell and animal studies to further evaluate its efficacy.
- Scientists are pursuing many different strategies to develop new therapeutics against the coronavirus. One area of interest is developing antibodies that bind to and inactivate viral proteins such as the spike protein, which coronaviruses use to enter human cells. A related approach uses small protein fragments called peptides instead of antibodies.
- The MIT team set out to engineer peptides that could strongly bind to the spike protein inside cells, and to use these peptides to trigger the cells to break down the viral proteins. Their idea was to have their peptides recruit naturally occurring proteins called E3 ubiquitin ligases, which can mark proteins for destruction when cells no longer need them.
- To generate their spike-protein-binding peptides, the researchers used a computational model of protein interactions that they had previously trained to optimize binding strength between two proteins. Chatterjee and others recently used similar computational methods to design improved versions of enzymes used for the genome-editing technique known as CRISPR. Their new CRISPR-Cas9 enzymes, together, can target more than 70% of DNA sequences, while the most commonly used form of CRISPR-Cas9 reaches only about 10%.
- In this case, the researchers used as their starting point the human ACE2 protein, which is found on the surface of certain types of human cells and binds to the coronavirus spike protein.
- They used their model to break ACE2 into many small fragments and then computationally predict how the fragments would interact with the spike protein. They instructed the model to optimize three features: First, they engineered peptides to have strong binding affinity to the spike protein. Second, they established that the peptides could bind well to other coronavirus spike proteins, in hopes that it could work against past and future strains of coronaviruses. Third, they ensured that the peptides would not bind strongly to human proteins called integrins, which are the proteins that normally bind to the ACE2 receptor in the body.
- This process generated about 25 candidate peptides, which the researchers fused to an E3 ubiquitin ligase and tested in human cells that expressed a fragment of the spike protein known as the receptor-binding domain (RBD).
- The best of these candidates, a 23-amino-acid peptide, broke down about 20% of the RBD proteins in the cells. However, this peptide did not work as well as the original ACE2 protein, which broke down about 30% of the RBD proteins. To improve the peptide’s performance, the researchers used their model to simulate how its RBD-binding would be affected if they substituted different amino acids at each of its 23 positions. That optimization process yielded a mutant peptide that improved the degradation rate to over 50%.
Tagged for destruction
- One key advantage of this peptide is its small size — even when fused to the E3 ubiquitin ligase, the entire chain is only around 200 amino acids in length. The researchers envision that RNA or DNA encoding the peptides could be delivered by harmless viruses called adeno-associated viruses.
- Another possibility would be to deliver the peptide on its own, allowing it to bind to the coronavirus spike protein outside of cells and be carried into cells with the virus. In that case, the virus would then be tagged for destruction as soon as it enters the cell, Chatterjee says.
- The researchers are now planning to test the peptide in human cells infected with the coronavirus, which will occur at specialized biosafety labs outside MIT. If those tests are successful, the researchers hope to test the peptide in animal models. They are also working on further improving the peptide so that it can bind the spike protein more strongly.
Note: The research described in this article has been published on a preprint server and has been submitted to a journal for peer review, but has not yet been peer-reviewed by scientific or medical experts.
3. Study is first to identify potential therapeutic targets for C19
- A team from Lawson Health Research Institute and Western University are the first in the world to profile the body’s immune response to C19. By studying blood samples from critically ill patients at London Health Sciences Centre (LHSC), the research team identified a unique pattern of six molecules that could be used as therapeutic targets to treat the virus. The study can be found at: Inflammation Profiling of Critically Ill Coronavirus… : Critical Care Explorations.
- Since the pandemic’s start there have been reports that the immune system can overreact to the virus and cause a cytokine storm – elevated levels of inflammatory molecules that damage healthy cells.
- “Clinicians have been trying to address this hyperinflammation but without evidence of what to target,” explains Dr. Douglas Fraser, lead researcher from Lawson and Western’s Schulich School of Medicine & Dentistry and Critical Care Physician at LHSC. “Our study takes away the guessing by identifying potential therapeutic targets for the first time.”
- The study included 30 participants: 10 C19 patients and 10 patients with other infections admitted to LHSC’s intensive care unit (ICU), as well as 10 healthy control participants. Blood was drawn daily for the first seven days of ICU admission, processed in a lab and then analyzed using statistical methods and artificial intelligence (AI).
- The research team studied 57 inflammatory molecules. They found that six molecules were uniquely elevated in C19 ICU patients (tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10 and elastase 2).
- The team also used AI to validate their results. They found that inflammation profiling was able to predict the presence of C19 in critically ill patients with 98% accuracy.
- They also found that one of the molecules (heat shock protein 70) was strongly associated with an increased risk of death when measured in the blood early during the illness.
- “Understanding the immune response is paramount to finding the best treatments,” says Dr. Fraser “Our next step is to test drugs that block the harmful effects of several of these molecules while still allowing the immune system to fight the virus.”
4. Early childhood vaccinations might protect children from C19
- A group of Lithuanian and Kurdish scientists have raised a hypothesis that the measles, mumps, and rubella (MMR) vaccine could protect children from C19. The hypothesis is based on the discovered sequence similarity of the 30 amino acid residues between glycoproteins of the coronavirus, measles and rubella viruses. An experimental analysis is required in order to support the hypothesis.
- An ongoing global pandemic of C19 has claimed more than 450 thousand lives already; globally, more than 9 million cases of C19 infection have been confirmed.
- According to detailed data of C19-infected patients from China, Italy, and South Korea, the disease is less common and milder in children younger than 10 years of age.
- The reasons why children are less susceptible to C19 remain unclear. However, the research carried out at Charmo University in Iraq and at Kaunas University of Technology (KTU) in Lithuania, provided evidence that MMR vaccination might be a reason why children have protection against the disease.
- The hypothesis is backed up by the sequence similarity data between the the coronavirus with both measles and rubella viruses.
- “The antibodies produced in children due to the MMR vaccine could recognize some protein parts (epitopes) on the coronavirus spike proteins. These antibodies, particularly in the epithelial layer of respiratory airways, block binding, and entering the virus into the cells”, explains Prof Rimantas Kodzius from KTU Panevezys Faculty of Technology and Business.
- The coronavirus is a single-strand, positive-sense RNA virus. S protein is a key immunogenic protein of the coronavirus that induces the host immune system; the latter fights off the foreign particles that enter the human body by producing antibodies. Humans are routinely immunized against several viral diseases in early childhood, which usually induces broad immunity against the viral particles.
- Immunological principle based on the antibody cross-reaction recognizing antigens in two different microbes inspired the group of scientists lead by Prof Kodzius of KTU, to look for homology sequence searching in the coronavirus and the viruses that commonly are prevented by vaccination during childhood.
- It was discovered that 30 amino acid residues share similarities between the Spike (S) glycoprotein of the coronavirus and the Fusion glycoprotein of Measles virus as well as with the envelope glycoprotein of the Rubella virus.
- “We are the first group to propose children protection through MMR vaccine and to support the claim by sequence homology between the coronavirus with measles and rubella viruses”, says Prof Kodzius.
- According to scientists, recent studies show that the levels of antibodies against MMR vaccination may persist for 15-20 years. Therefore, the protection against C19 could last up to 15-20 years.
- However, experimental research including testing purified spike protein of the coronavirus against the polyclonal and monoclonal antibodies of measles and rubella viruses in vivo and in vitro is required in order to support the hypothesis.
5. Scientists Warn About Transmission or Coronavirus to Animals and then Back to People
- As evidence mounts for the possibility of the coronavirus infecting various animals, scientists at UCL say a global effort is needed to reduce the risk of the virus later returning to people.
- In a comment piece for The Lancet Microbe, researchers write that if the virus becomes common in an animal population that lives near people, such as pets or livestock, there would be a risk that another outbreak could occur even if the virus is eradicated in people in the area.
- The authors call for more research into which animals are susceptible to the coronavirus and suggest implementing a surveillance program to regularly test animals that could pose the highest risks of transmission.
- Co-author Professor Joanne Santini (UCL Structural & Molecular Biology) said: “There is increasing evidence that some animals can catch the coronavirus from people, and might subsequently transmit it to other people — but we don’t know just how much of a risk this is, as it’s an area of study that has not yet been prioritized.
- “We need to develop surveillance strategies to ensure we don’t get taken by surprise by a large outbreak in animals, which could pose a threat not just to animal health but to human health as well.
- “Virus transmission in animal populations could become irreversible if left unchecked, and may threaten the success of existing public health measures if people continue to catch the virus from an infected population of animals.”
- The authors write that the immense scale of the C19 pandemic compounds the possibility of sufficient animals becoming ‘reservoirs’ of the virus, which could be more likely than for past epidemics, such as the more contained SARS-CoV-1 outbreak in 2002-2003.
- Professor Santini and co-author Professor Sarah Edwards (UCL Science & Technology Studies) reviewed evidence from case studies, experiments testing infection in small groups of animals, as well as laboratory and modelling studies describing likely infection mechanisms.
- Modelling and lab studies suggest that the coronavirus could in theory be transmitted to numerous animals, based on findings that the spike protein on the virus attaches to host cells, using a protein that is found in many different species.
- The research paper advises that, once scientists identify which animals could become infected, they then need to figure out whether they will become unwell or remain asymptomatic, and whether an infected individual is able to then transmit the virus to other animals or even to humans.
- Notably, there have been recent cases in the Netherlands of farmed mink becoming infected with the coronavirus, leading to two people catching the virus from these animals, in an outbreak that has led to thousands of mink being culled. The researchers say this example highlights not only the risk to human health, but also animal welfare concerns and potential loss of livelihoods in the agricultural sector.
- Professor Edwards commented: “There’s an urgent need for widespread surveillance, by testing samples, preferably non-invasively, from large numbers of animals, particularly pets, livestock and wildlife that are in close proximity to human populations. More laboratory experiments on small numbers of animals are unlikely to give us the evidence needed to be confident that certain species are entirely safe, making major surveillance work the only real option here.
- “We need more information, at the same time as taking simple precautionary measures especially with species which have the potential to spread the virus rapidly in the wild. A robust risk assessment would also require reviewing our ability to manage an outbreak in those animals, namely our ability to isolate, protect, or contain different animals.”
1. Rise of the Biohackers: Do It Yourself Vaccine
A vaccine for the coronavirus may work in monkeys. Now a California biohacker plans to test it on himself.
- As C19 continues its march around the globe, scientists have embarked on an unprecedented campaign to develop a vaccine against the disease. There are more than 125 potential vaccines undergoing tests, with 20 in human trials. And the U.S. program, Operation Warp Speed, has set the ambitious goal of a vaccine for early 2021.
- But that unheard-of pace in vaccine development isn’t fast enough for Josiah Zayner, a one-time NASA scientist who left mainstream science to proselytize the value of do-it-yourself home experiments.
- “This is the perfect opportunity for biohackers,” he said. “We can move science faster.”
- Zayner is infamous in some circles for attention-grabbing experiments that have included injecting himself with the gene-editing tool Crispr while giving a talk at a San Francisco biotech conference. So on May 20, when a group of researchers from institutions including Harvard University published a paper demonstrating a DNA vaccine that appeared to trigger protective immunity against the coronavirus, Zayner saw an opportunity.
- “They said specifically what they used, which is really easy to recreate,” he said, speaking from the West Oakland, California, headquarters and lab of his biohacking supply company, The Odin. “You know, it works in monkeys. Let’s test it on humans.”
- He intends to not only reproduce the monkey experiment in humans, but also, along with two collaborators in Mississippi and Ukraine, livestream the entire process over the course of several weeks with the aim of showing others the ease with which such scientific findings can be reproduced. They have nicknamed the endeavor Project McAfee, after the antiviral software. The corresponding authors of the study Zayner is basing his DIY experiment on declined comment on his plan to test the vaccine on himself.
- Zayner has a loyal following. The fast-moving science of genome editing has made engineering biology increasingly simple, in some cases as easy as rewriting a piece of computer code. And a growing cadre of DIY types have argued that this cutting-edge science should be easily available to anyone outraged by exorbitant drug prices — or anyone simply curious to give such experiments a whirl at home.
- But these DIY experiments haven’t always gone according to plan, and that’s raised safety worries among established scientists.
- “Even if he does it well, people copying him poorly could be hurt. And for what?,” said Hank Greely, a Stanford University bioethicist. “Uncontrolled experiments with doubtful, non-standardized ingredients and conditions are not likely to lead to scientific knowledge that will produce vaccines faster.”
- What enables a DIY enthusiast like Zayner to reproduce such an experiment is a proliferation of new scientific tools, alongside companies that allow most anyone to simply order up, say, viral DNA on the internet and have it delivered ready-to-go to their home. In the rhesus macaque experiment, researchers developed an array of so-called DNA vaccines, which use select portions of a virus’ genetic code in an attempt to trigger an antibody-producing immune response from the body, and thus hopefully generate immunity to the virus.
- In the case of the coronavirus, it is the crown-like spike protein that causes the body to move into action, so researchers developed vaccines expressing different forms of that protein and tested them in 35 monkeys. The results were encouraging: The vaccinated monkeys developed antibodies to the virus and one version of the vaccine appeared able to fend off the virus.
- From a DNA synthesis company Zayner was able to order offline the same spike protein sequence that the researchers had used, and have it put in a solution that would allow him to inject the vaccine into his muscles.
- “With the pandemic, there’s so many tools available to purchase commercially from companies, it creates a perfect opportunity for biohackers to test something like this out on humans,” he said. “That’s the logical next step.”
- Generally, after trials in monkeys, the next step in vaccine development is to give the vaccine to a small number of people in order to test its safety and dosage, as well as to confirm whether it actually stimulates the human immune system. Zayner and his collaborators have, in essence, volunteered themselves for this task.
- “I would like to see a future where biotech is less arcane,” said David Ishee, a self-taught scientist in Mississippi and a collaborator on the project. “But the most realistic thing that will come of this is that maybe people will understand the news they’re reading better.”
- The trio plan to test the vaccine in human cells to ensure those cells produce the spike protein. Then, they will inject themselves with the vaccine, and perform antibody tests on themselves regularly to monitor whether their bodies develop an immune response. All three experimenters were tested at a commercial lab beforehand to ensure they don’t already have antibodies to the virus.
- “If he has and uses the appropriate biosafety precautions, I see nothing wrong with his efforts to replicate the macaque work in living human cells,” said Greely, the Stanford bioethicist. “If he can do that, it might be a somewhat useful scientific finding.”
- Moving the work into humans, though, Greely said, seems less useful.
- “At best he’ll have three people who have received this DNA vaccine,” he said. “It’s hard for me to see his administration of a vaccine to three people as producing any useful scientific knowledge, except perhaps in the unhappy result that they have terrible reactions to it. But even then, it’s just anecdotal, a caution but not a proof.”
- So long as they only provide information about how to make a DIY vaccine, rather than distributing the materials to make one, Zayner’s efforts do not fall strictly under the regulatory purview of the Food and Drug Administration, said Patricia Zettler, a former FDA attorney and law professor at Ohio State University. Still, said Zettler, the FDA has cracked down on unproven and unauthorized C19 products, and so these efforts might attract the agency’s attention. Last year, a complaint prompted the California Medical Board to investigate whether Zayner was practicing medicine without a license, though that investigation was ultimately dropped.
- Zayner has been criticized in the past for playing a role that is part performance artist, part scientist. Many a biohacker has demonstrated a flair for the dramatic, with daredevil stunts such as live-streamed DIY therapy injections. Zayner wants the movement to move beyond that. His biggest hope for Project McAfee is that it will demonstrate to people that they can undertake many scientific experiments at home using good scientific methodology.
- Zayner has created an online course entitled Do-It-Yourself: From Scientific Paper to C19 DNA Vaccine so that his viewers may follow along with his work. In the past, his company has hosted online biohacker bootcamp courses, which he says have become The Odin’s most popular offering.
- “I want people to learn something from this,” he said, “So it’s no longer this big black box of what science, clinical trials and all this stuff is.”
2. Sanofi, a straggler in the C19 vaccine race, accelerates its plans
- The drug maker Sanofi Pasteur has been more cautious than some of its rivals in projecting when its C19 vaccines might be ready. Now, it’s announcing an acceleration of clinical trials to reach the market faster — and striking a $425 million deal to broaden its partnership with a smaller biotech company to develop one of them.
- The start of a Phase 1/2 clinical trial for a vaccine that Sanofi is developing with GSK has been pushed up to September from December. And a first-in-human study of the vaccine it is developing with Translate Bio, based on mRNA technology, will begin in the fourth quarter, Sanofi said Tuesday.
- Sanofi, which has deep experience in vaccinology but has had one of the more conservative timelines of the major players in the race to develop C19 vaccines, is now predicting it will be able to catch up to competitors that got off to an earlier start in clinical trials than it did.
- “We are the only vaccine in the race that’s off a proven platform that works in scale,” CEO Paul Hudson said of the vaccine Sanofi is making with GSK’s help.
- The vaccine, which Sanofi expects to reach the market sooner than the vaccine it is partnering with Translate Bio on, employs the approach used to make the company’s flu vaccine, Flublok, called a recombinant vaccine. Genetic material from the surface protein of the coronavirus is inserted into insect cells, which express antigen that is then purified.
- The company said its experience working with the recombinant platform will help as it ramps up production.
- Sanofi is using one of GSK’s proprietary adjuvants — a compound that boosts the immune response, allowing less vaccine to be used for each person — with this vaccine.
- When Sanofi announced it was entering the race to develop C19 vaccines back in mid-February, it estimated it would take three to four years to develop a product. It is now predicting it may be able to win approval for two vaccines in 2021.
- “Things have matured a lot from where we were,” John Shiver, senior vice president for global vaccines, said of the compressed timelines.
- Sanofi believes it will have enough data from its Phase 1/2 trial for the recombinant vaccine that it could be used via the Food and Drug Agency’s emergency use pathway, if the agency issues such approvals for C19 vaccine. The Phase 3 trial for that vaccine could begin in December or January, Shiver said, with a goal of having the vaccine fully licensed by June.
- Sanofi, which like others working on C19 vaccines is producing in bulk at risk — before its candidate vaccines have been shown to work — expects to have 100 million doses of the recombinant vaccine by the end of 2020, and an additional 1 billion doses in 2021, he said.
- It’s unclear how many shots will be required to protect each person, though the company expects it may take two, with a four-week interval between the vaccinations.
- If that proves to be the case — and if the vaccine works — Sanofi could provide enough of this vaccine to protect 50 million people in 2020 and 500 million in 2021.
- Translate Bio and Sanofi signed a collaboration deal in 2018 to develop mRNA vaccines for as many as five infectious diseases. The partnership was first expanded in March to pursue the development of an mRNA vaccine against C19. The second expansion, announced Tuesday, essentially gives Sanofi an exclusive license to pursue the development of mRNA vaccines made by Translate Bio across all infectious disease areas.
- “This leverages a lot of the great work going on between the two companies. We’ve generated a significant amount of data across some of the initial pathogens we started working on. We felt it was prudent to put this platform to work against infectious disease vaccines more broadly,” said Translate Bio CEO Ron Renaud.
- Under terms of the new deal, Sanofi is paying Translate Bio $300 million in cash and will purchase $125 million in company stock at $25.59 per share, representing a 58% premium to Tuesday’s closing price.
- Translate Bio will be eligible for up to $1.9 billion in future milestone payments, including payments tied to the development of a C19 vaccine. If any of these mRNA vaccines reach the market, Sanofi will pay Translate Bio royalties based on sales.
- Sanofi and Translate Bio have multiple mRNA vaccine candidates against C19 in preclinical testing now, with the goal of selecting a lead candidate for a first-in-human study to start in the fourth quarter. That still puts them behind competing mRNA vaccines from Moderna and a partnership of Pfizer and BioNTech that have already begun clinical trials.
- A second mRNA vaccine program against influenza is also in preclinical testing, with a human study expected to start in the middle of 2021.
3. The Race for a Vaccine: Will Collaboration Trump the Desire to Win?
- A Chinese company will turn to Brazil for help. The World Health Organization (WHO) is adopting a strategy forged in a war zone during an Ebola outbreak. And the Trump administration plans to lean on existing infrastructure for testing HIV and flu vaccines. These are the disparate strategies about to be employed in the next and most important stage of the C19 vaccine race: the large-scale, placebo-controlled, human trials needed to prove which of the more than 135 candidates are safe and effective.
- Two such efficacy trials plan to start next month, even as the United States and global initiatives struggle to answer major questions, from what it means for a C19 vaccine to work to how to find enough people exposed to the virus so a candidate can be put to a real-world test. Populations that have high levels of viral transmission are a moving target—Wuhan, Seattle, or Milan might once have been a good place to test the mettle of a vaccine, but no longer. And quickly enrolling tens of thousands of properly informed people who meet a trial’s entry criteria is a “big lift,” says Susan Buchbinder, an epidemiologist at the San Francisco Department of Public Health who runs vaccine trials.
- Competition among trial efforts could hinder the global push, says Wayne Koff, who heads the nonprofit Human Vaccines Project and formerly led the HIV vaccine program at the National Institute of Allergy and Infectious Diseases (NIAID). “It’s absolutely extraordinary how much has been done in 6 months, but there’s an old adage that everybody loves to collaborate unless they want to win.” Others, however, don’t anticipate conflicts, noting that scientists and officials are sharing information about trial designs and plans. “Each one will contribute differently,” says Ana Maria Henao Restrepo, lead representative of WHO’s vaccine effort, Solidarity. “I don’t see competition.”
- “Winning,” one of U.S. President Donald Trump’s favorite terms, is the clear goal of Operation Warp Speed, the U.S. project that aims to start to vaccinate millions of Americans in October and offer shots to 300 million people in the United States by January 2021. After winnowing down vaccine candidates in an opaque process over the past month and committing what could be more than $2 billion to its top choices, Warp Speed plans to enter three to five of them into efficacy trials that will have “harmonized” protocols to streamline oversight and will run analyses in central labs so data can more easily be compared.
- The first Warp Speed candidate to launch, from the biotech Moderna, is composed of RNA encoding the coronavirus spike protein from the coronavirus. The candidate’s efficacy trial, announced by the company on 11 June, will enroll 30,000 people and take place at established HIV and flu vaccine test sites, primarily at U.S. hospitals and universities, now overseen by Warp Speed. But which of those brick-and-mortar sites will have enough coronavirus circulating near them to quickly produce an efficacy signal is uncertain given the shifting distribution of new cases in the United States.
- China has an even starker problem: There’s currently little transmission to speak of in the country, which has forced Sinovac Biotech, a company based in Beijing, to stage efficacy trials of its vaccine candidate in Brazil, where the C19 epidemic is now raging. With a product composed of the entire virus, inactivated with chemicals, Sinovac announced this week it is collaborating with the Butantan Institute, a major research institution in São Paulo that manufactures vaccines. “We are working very hard to start the trial in July,” says Sinovac Senior Director Meng Weining.
- WHO proposes a different solution for Solidarity’s efficacy trials. The agency hasn’t yet announced which candidates Solidarity will test, but, unlike Warp Speed—which won’t consider Chinese-made vaccines—it is open to products from every country and has made public detailed criteria for how it will prioritize vaccines.
- To cope with the patchiness of the pandemic, Solidarity will adopt a strategy Henao Restrepo helped develop for Ebola vaccine trials in Guinea in 2015 and, 3 years later, in the Democratic Republic of the Congo (DRC): setting up vaccination teams that can quickly mobilize to localized outbreaks.
- “We did this in Congo despite the war,” Henao Restrepo says. “It’s not the traditional way, and some people think that we are crazy, but we have done it not once but twice.” In the DRC, about 20 teams with 15 members each drove around the affected regions and set up temporary sites, vaccinating and following more than 300,000 people.
- Warp Speed, which could if needed expand its trials to international sites used for HIV drug and vaccine testing, also plans to form “surge clinics” to quickly recruit people in rural U.S. areas with big outbreaks or pockets of high transmission such as nursing homes. Models driven by machine learning will help Warp Speed forecast where infection will be highest, says Peter Gilbert, a University of Washington, Seattle, biostatistician. “There are risk predictors that account for space and geography and features that are more constant like race, ethnicity, or preexisting conditions,” Gilbert says. “It’s really complicated.”
- One of the trickiest issues for trial designers is deciding what, exactly, represents success for a C19 vaccine. “Is it an infection endpoint, a transmission endpoint, preventing moderate disease, or preventing severe disease?” Koff asks.
- “There was a lot of debate on that question,” for Warp Speed, notes John Mascola, who heads NIAID’s Vaccine Research Center and contributes to the project. A C19 vaccine that fails to prevent infection might still provide great benefit if it reduces symptomatic disease, so Warp Speed and Solidarity both ultimately chose that as the primary endpoint of the trials. Trial volunteers who develop fever, headache, dry cough, or other symptoms linked to C19 will be tested for the coronavirus, to see whether more people with confirmed infections develop symptomatic disease in the placebo arm of the trial than among those who received the vaccine.
- To detect an efficacy signal, both Warp Speed and Solidarity estimate they will need to give each vaccine to 15,000 to 20,000 people in a population that has a 1% per year incidence of the coronavirus infection. If the vaccine prevents C19 symptoms at least 50% of the time, its efficacy should be clear in 6 months, after about 150 infections have accumulated in the trial.
- Both efforts will pit multiple vaccine candidates head to head. One difference is that Solidarity plans to compare all its vaccines against a shared placebo group, an approach that reduces the number of volunteers the researchers need to recruit and follow. “In the Solidarity trial, the philosophy is we have to make this thing really simple,” says Gilbert, who has worked with this effort, too. Solidarity trial sites have the option to do nuanced studies on immunity and other issues, but those are built into Warp Speed’s trials. They will do repeated blood draws and nasal or throat swabs to evaluate immune responses and viral levels. The data might help researchers understand why vaccines succeed or how they might affect transmission.
- In addition to Solidarity, WHO is helping the Access to C19 Tools (ACT) Accelerator, another global effort, which may stage its own vaccine efficacy trials if companies do not want to participate in Solidarity. “Companies may or may not be very enthusiastic about head-to-head comparisons,” explains Soumya Swaminathan, WHO’s chief scientist and top liaison to the ACT Accelerator. And the ACT Accelerator has pockets as deep as Warp Speed: Countries and philanthropies in May pledged $8 billion, with a commitment that it would equitably distribute any proven C19 products—vaccines, treatments, diagnostics—to rich and poor alike.
- Buchbinder is impressed by the speed at which these massive efforts have gotten underway. “It’s unlike any other research I’ve undertaken,” she says. But she and others are careful to temper expectations. Even though she will oversee a Warp Speed trial site, for example, she doubts the U.S. effort will meet Trump’s goal of having a proven vaccine by October. Koff agrees; the failures of so many HIV vaccine trials have sobered him, he says. “We need to be really careful how we manage expectations,” he concludes.
G. Concerns & Unknowns
1. CDC broadens guidance on Americans facing risk of severe C19
- The Centers for Disease Control and Prevention on Thursday broadened its warning about who is at risk of developing severe disease from C19 infection, suggesting even younger people who are obese or have other health conditions can become seriously ill if they contract the virus.
- The new advice, timed to influence behavior going into the July 4 weekend, came as CDC Director Robert Redfield acknowledged serology testing the agency has conducted suggests about 20 million Americans, or roughly 6% of the population, has contracted C19. Redfield said for every person who tests positive, another 10 cases have likely gone undiagnosed. [Note: if 20,000,000 Americans have been infected and approx. 127,000 have died, that would imply an infection fatality rate of 0.635%, which would be considerably higher than the 0.1% fatality rate for the flu. It is also considerably higher than the CDC’s previous estimate of the fatality rate.]
- While the 20 million estimate is far higher than the figure on the CDC’s C19 website, it still represents a fraction of the country’s population, Redfield said.
- “This pandemic is not over. The most powerful tool that we have, a powerful weapon, is social distancing,” he insisted during a press conference, only the second the CDC has been allowed to conduct since early March.
- The new advice frames the risk as rising with age, jettisoning earlier warnings that mainly those 65 and older faced higher risk. It also puts greater emphasis on the risk presented by a number of health conditions, including having a body mass index of 30 or over. Previously the warning related to people who had a BMI of 40 or over.
- “Younger people are in no way completely immune to the effects of the coronavirus nor are they at zero risk of severe manifestations,” said the Jay Butler, incident manager for the CDC’s C19 response. “And among young people, that risk is elevated in those with underlying illness or health conditions, including things like diabetes or obesity.”
- The agency is also warning that being pregnant may increase a woman’s risk of being hospitalized and having a severe bout of the illness, based on a study of more than 8,000 pregnant women in the United States who were diagnosed with C19.
- The study, published in the CDC’s Morbidity and Mortality Weekly Report, an online journal, found that pregnant women were 50% more likely to be hospitalized with C19 than infected women who weren’t pregnant and had a 70% greater chance of needing mechanical ventilation than non-pregnant women with the infection.
- But the study did not find an increased risk of death among the pregnant women.
- The new guidance reflects what has been apparent for months now, with countless new severe cases among young people and those with underlying conditions. But warnings of those cases have largely gone unheeded as states have begun to reopen.
- The country is seeing a fresh surge of cases, particularly in the West and South, where hospitals are swelling with new cases and state governments are struggling to respond. On Thursday, Texas Gov. Greg Abbott announced the state would pause its reopening in the face of outbreaks across the state.
- Despite the surge in cases, President Trump has continued to express the view that the virus is going away. When asked if Americans were getting mixed messages about whether they need to take precautions to prevent becoming infected, the CDC director appeared to seek a middle ground.
- Redfield suggested many of the infections now being diagnosed would have been missed earlier in the pandemic, when testing was less common.
- “I’m asking people to recognize that we’re in a different situation today than we were in March, in April, where the virus was being disproportionately recognized in older individuals with significant comorbidities and was causing significant hospitalizations and deaths,” he said.
- “Today we’re seeing more virus. It’s in younger individuals. Fewer of those individuals are requiring the hospitalizations and having a fatal outcome. But that is not to minimize it.”
- But Redfield went on to note that descriptions of the state of the pandemic in the country can be misleading, with maps that show where transmission is high suggesting much of the nation is experiencing high levels of spread. In reality, he said, about 110 or 120 counties in the country currently have significant transmission. There are more than 3,100 counties in the United States.
- The new guidance breaks down medical conditions that can influence disease severity into those for which there is strong evidence, and those for which the evidence is not as strong, classifying the latter as conditions that might increase the risk of severe illness.
- Cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease or COPD, obesity, any immuno-suppressing condition, sickle cell disease, a history of an organ transplant, and type 2 diabetes are classified as having strong evidence of increasing the risk of C19 infection.
- Conditions that are considered ones that might increase the risk of severe illness are chronic lung diseases, including moderate to severe asthma and cystic fibrosis, high blood pressure, a weakened immune system, neurologic conditions, such as dementia or history of stroke, liver disease, and pregnancy.
2. The coronavirus is leaving some people with permanent lung damage
- People infected with the coronavirus may be left with permanent lung damage. Doctors are reporting growing numbers of people who still have breathlessness and coughing months after falling ill with C19, and whose chest scans show evidence of irreversible lung scarring.
- The numbers of people affected aren’t yet known, but estimates are as high as one in five of those who needed intensive care treatment for C19. Permanent damage is sometimes seen after other kinds of chest infections that can cause similar lung inflammation to the coronavirus, such as flu and pneumonia.
- “We have always seen this before – what’s different is the scale of this,” says James Chalmers, a chest physician and adviser to the British Lung Foundation. Previously, his clinic in Scotland would have seen post-infection scarring of the lungs just once or twice a year, he says. “Now we are seeing dozens of patients coming through.”
- In a study in Italy, which was one of the first European countries to be hit by the coronavirus, doctors are scanning the lungs of people three months after they fell ill. Although the full results aren’t yet in, Paolo Spagnolo at the University Hospital of Padua estimates that 15 to 20% of those treated in intensive care at his hospital for C19 have scarring. “We have to be prepared in the future to manage these patients.”
- In most people, the coronavirus causes only mild symptoms, but in some it leads to serious lung inflammation and an excess of immune signalling chemicals, leading to a complication called a cytokine storm. “If left unchecked, the inflammation starts to cause damage and scarring,” says Chris Meadows, an intensive care doctor at Guy’s and St Thomas’ NHS Foundation Trust in London.
- If someone is left with scarring, also known as fibrosis, there is no way to reverse it, says Chalmers. All people can do is try to improve their aerobic fitness to compensate for their lower lung function and learn to cope with breathlessness.
- As well as scarring, there may be other mechanisms that cause long-term problems. Severe C19 makes blood more prone to clotting, so people develop tiny clots in the blood vessels of their lungs. To compensate, new blood vessels grow, but these can be disorganised, leading to high blood pressure in their lungs. “You don’t get as much oxygen,” says Chalmers.
- Lung damage isn’t confined to people who needed ventilation, he says. “More severe covid means more likelihood of permanent damage, but I have got a couple of patients who were not on ventilators and have long-term complications.”
3. Mounting clues suggest the coronavirus might trigger diabetes
Evidence from tissue studies and some people with C19 shows that the virus damages insulin-producing cells.
- In mid-April, Finn Gnadt, an 18-year-old student from Kiel, Germany, learnt that he had been infected with the coronavirus despite feeling well. Gnadt’s parents had fallen ill after a river cruise in Austria, so his family was tested for virus antibodies, which are produced in response to infection.
- Gnadt thought he had endured the infection unscathed, but days later, he started to feel worn out and exceedingly thirsty. In early May, he was diagnosed with type 1 diabetes, and his physician, Tim Hollstein at the University Hospital Schleswig-Holstein in Kiel, suggested that the sudden onset might be linked to the viral infection.
- In most people with type 1 diabetes, the body’s immune cells start destroying β-cells — which are responsible for producing the hormone insulin — in the pancreas, often suddenly. In Gnadt’s case, Hollstein suspected that the virus had destroyed his β-cells, because his blood didn’t contain the types of immune cells that typically damage the pancreatic islets where the β-cells live.
- Diabetes is already known to be a key risk factor for developing severe C191 and people with the condition are more likely to die. “Diabetes is dynamite if you get C19,” says Paul Zimmet, who studies the metabolic disease at Monash University in Melbourne, Australia.
- Now Zimmet is among a growing number of researchers who think that diabetes doesn’t just make people more vulnerable to the coronavirus, but that the virus might also trigger diabetes in some. “Diabetes itself is a pandemic just like the C19 pandemic. The two pandemics could be clashing,” he says.
- Their hunch is based on a handful of people such as Gnadt, who have spontaneously developed diabetes after being infected with SARS-CoV-2, and on evidence from dozens more people with C19 who have arrived in hospital with extremely high levels of blood sugar and ketones, which are produced from fatty deposits in the liver. When the body doesn’t make enough insulin to break down sugar, it uses ketones as an alternative source of fuel. “In science, sometimes you have to start off with very small evidence to chase a hypothesis,” says Zimmet.
- Researchers cite other evidence, too. Various viruses, including the one that causes severe acute respiratory syndrome (SARS), have been linked with autoimmune conditions such as type 1 diabetes. And many organs involved in controlling blood sugar are rich in a protein called ACE2, which SARS-CoV-2 uses to infect cells.
- The latest clue comes from an experimental study in miniature lab-grown pancreases published last week suggests that the virus might trigger diabetes by damaging the cells that control blood sugar.
- But other researchers are cautious about such suggestions. “We need to keep an eye on diabetes rates in those with prior C19, and determine if rates go up over and above expected levels,” says Naveed Sattar, a metabolic-disease researcher at the University of Glasgow, UK.
- To establish a link, researchers need more robust evidence, says Abd Tahrani, a clinician–scientist at the University of Birmingham, UK. “Well-constructed epidemiological cohort studies and mechanistic and experimental studies are needed,” he says.
- One initiative is now under way. Earlier this month, an international group of scientists, including Zimmet, established a global database to collect information on people with C19 and high blood-sugar levels who do not have a history of diabetes or problems controlling their blood sugar.
- Cases are beginning to trickle in, says Stefan Bornstein, a physician at the Technical University of Dresden, Germany, who also helped to establish the registry. The researchers hope to use the cases to understand whether SARS-CoV-2 can induce type 1 diabetes or a new form of the disease. And they want to investigate whether the sudden-onset diabetes becomes permanent in people who’ve had C19. They also want to know whether the virus can tip people who were already on their way to developing type 2 diabetes into a diabetic state.
- The study in pancreatic organoids shows how SARS-CoV-2 could be damaging the organ. Shuibing Chen, a stem-cell biologist at Weill Cornell Medicine in New York City, and her colleagues showed that the virus can infect the organoid’s α- and β-cells, some of which then die. Whereas β-cells produce insulin to decrease blood-sugar levels, α-cells produce the hormone glucagon, which increases blood sugar. The virus can also induce the production of proteins known as chemokines and cytokines, which can trigger an immune response that might also kill the cells, according to the study published in Cell Stem Cell on 19 June.
- Chen says the experiments suggest that the virus can disrupt the function of key cells involved in diabetes — either by directly killing them or by triggering an immune response that attacks them.
- The virus also attacked pancreatic organoids that had been transplanted into mice, and cells in liver organoids. The liver is important for storing and releasing sugar into the blood stream when it senses insulin.
- The organoid study adds strength to the argument that SARS-CoV-2 might cause or worsen diabetes, but the paper itself is not enough to prove the link, says Tahrani.
- There could be more going on than some scientists suggest, says Shane Grey, an immunologist at the Garvan Institute of Medical Research in Sydney, Australia. The virus could trigger an extreme inflammatory state, which would impair the ability of the pancreas to sense glucose and release insulin, and dampen the ability of the liver and muscles to detect the hormone, he says. This could trigger diabetes.
- Fatigue and muscle loss caused by severe infection can also push people at risk of the condition into a pre-diabetic state, says Sattar. Only long-term studies will reveal what’s really going on, he says.
4. Study Raises Concerns for Pregnant Women With the Coronavirus
- Pregnant women infected with the coronavirus are more likely to be hospitalized, admitted to an intensive care unit and put on a ventilator than are infected women who are not pregnant, according to a new government analysis.
- Pregnant women are known to be particularly susceptible to other respiratory infections, but the CDC has maintained from the start of the pandemic that the virus does not seem to “affect pregnant people differently than others.”
- The increased risk for intensive care and mechanical ventilation worried experts. But the new study did not include one pivotal detail: whether pregnant women were hospitalized because of labor and delivery. That may have significantly inflated the numbers, so it is unclear whether the analysis reflects a true increase in risk of hospitalization.
- Admission for delivery represents 25% of all hospitalizations in the United States, said Dr. Neel Shah, an assistant professor of obstetrics and gynecology at Harvard University. Even at earlier stages of pregnancy, doctors err on the side of being overly cautious when treating pregnant women — whether they have the coronavirus or not.
- “There’s quite clearly a different threshold for hospitalizing pregnant people and nonpregnant people,” he said. “The question is whether it also reflects something about their illness, and that’s something we don’t really know.”
- The results are to be published on Thursday by the CDC; government researchers presented the data to a federal immunization committee on Wednesday. (The slides were posted online on Wednesday afternoon but taken down later in the day.)
- The analysis, the largest of its type so far, is based on data from women with confirmed infections of the coronavirus as reported to the CDC by 50 states and Washington, from Jan. 22 to June 7.
- The report includes information on 8,207 pregnant women between ages 15 to 44, who were compared to 83,205 women in the same age bracket who were not pregnant.
- More than 31% of the pregnant women were hospitalized, compared with about 6% of women who were not pregnant. Pregnant women were more likely to be admitted to the I.C.U. (1.5% versus 0.9%) and to require mechanical ventilation (0.5% versus 0.3%).
- These proportions are small, Dr. Shah noted, and the 10-fold difference in the number of pregnant and nonpregnant women in the analysis makes it difficult to compare their risks.
- In a separate analysis by Covid-Net of women hospitalized with the coronavirus, CDC researchers noted that “the risk of I.C.U. and mechanical ventilation was lower among pregnant compared to nonpregnant women.” Covid-Net analyzes data from hospitalizations in the network’s surveillance area in 14 states.
- Despite the ambiguities, some experts said the new data suggests at the very least that pregnant women with the coronavirus should be carefully monitored.
- If many of the pregnant women were hospitalized for labor and delivery, the proportion of women who were hospitalized for only coronavirus infection and became severely ill — those advancing to the I.C.U. or ventilation — would be even higher, said Dr. Denise Jamieson, head of the C19 task force at the American College of Obstetricians and Gynecologists.
- “I think the bottom line is this: These findings suggest that compared to nonpregnant women, pregnant women are more likely to have severe Covid,” she said.
- Pregnancy transforms the body’s biology, ramping up metabolism, blood flow, lung capacity and heart rate. It also suppresses a woman’s immune system to accommodate the fetus — a circumstance that can increase her susceptibility to respiratory illnesses like influenza.
- Because of this heightened risk, scientists have been closely monitoring pregnancy outcomes in various coronavirus studies. So far, few studies have indicated a significant risk for pregnant women or for their children. Infections in newborns have been exceedingly rare.
- Still, as the pandemic has progressed, prenatal care has been severely disrupted, Dr. Shah said, and women are being hospitalized for conditions that might have been caught and treated much earlier.
- “Things that might have happened in an office setting are happening in a hospital triage setting,” he said.
- Dr. Jamieson pointed to a recent study of pregnant women at New York City hospitals who were asymptomatic at admission. Of the 241 women who tested positive for the coronavirus in that study, 48 did not have symptoms at first but then became severely ill.
- The study also found that women with more severe symptoms were more likely to give birth prematurely.
- “All this information points to the importance of being vigilant when it comes to monitoring pregnant women,” Dr. Jamieson said. “They’re not at as great a risk as, for example, older people, or people with other underlying medical conditions. But they do seem to be at some increased risk.”
- The data suggests that hospitals should aim to test all pregnant women for the coronavirus, regardless of symptoms, she added. The new analysis also has implications for a coronavirus vaccine, whenever one becomes available.
- “How strongly are we going to counsel pregnant women about the benefits of vaccines?” Dr. Jamieson wondered.
5. Preventing dangerous blood clots from C19 is proving tricky
- For some severely ill C19 patients, the struggle to take in enough air is not only due to having fluid-clogged lungs. The quest for oxygen also is stymied by a plethora of blood clots.
- As it’s become clear that excessive clotting can be a complication of a serious coronavirus infection, there’s been debate over how best to manage the blockages. Now clinical trials are under way to assess different doses of anticoagulants, medicines already used to prevent or break up blood clots in other patients. But it’s not as easy as “the more, the better” since, in general, higher doses come with higher risks of major bleeding.
- Striking the right balance between clotting and bleeding is something the body itself does regularly, and not just after an injury. Infections spur clotting too. That’s because the immune system, inflammation and clotting are linked.
- If the regulation of these systems gets out of whack, the scales can tilt toward thromboinflammation, in which severe inflammation leads to excessive clotting. For C19 patients, that’s happening to an alarming degree.
- But the dose of anticoagulant used to prevent blood clots in other patients, at risk after surgery or other procedures, is not working for coronavirus-related clotting. Figuring out if there is an effective dose and the best time to treat could be one part of helping C19 patients.
- Why clotting can be a complication of a serious infection is rooted in its role in the immune system. Although well known for stopping catastrophic bleeding at the site of a cut, there’s more to clotting than just plugging leaks. Clots can also trap pathogens, preventing them from invading tissues and traveling throughout the body.
- When the innate immune system — the body’s first defense against pathogens — becomes alert to an invader, the body begins releasing proteins that ramp up inflammation, and certain immune cells activate the clotting system. Pathogens get trapped in a clot like a fly in a spider web, held fast until immune cells come in for the kill.
- But for some C19 patients, the clotting response becomes excessive, putting their lives at risk when blood vessels become blocked. Pulmonary embolisms, which happen when a clot breaks free from a vein and gets stuck in the lungs, are common in these patients. The clots are also happening at the level of the smallest blood vessels, which disrupts the delivery of oxygen, damaging organs.
- “It’s the people who get really sick who seem to have the worst problem with developing blood clots,” says clinical hematologist Jean Connors of Harvard Medical School and Brigham and Women’s Hospital in Boston. Some of these patients “have such a dramatic immune response” and heightened inflammation, which in turn leads to severe clotting, she says.
- And the clotting appears to be worse than that experienced by patients with different diseases but a similar severity of illness. A small autopsy study that compared the lungs of patients who died from either C19 or from influenza A (H1N1) in 2009 suggests that clots were a bigger problem with the coronavirus. Clotting in the tiny blood vessels associated with the alveoli, the little air sacs that allow the exchange of oxygen between the lungs and the blood, was widespread in the lungs of seven C19 patients compared with the lungs of seven influenza patients, researchers reported May 21 in the New England Journal of Medicine.
- The lungs of C19 patients in the autopsy study also revealed gravely injured endothelial cells, which line blood vessels. These cells normally keep clots at bay so that blood can flow smoothly. But “the virus seems to cause damage to the lining of the blood vessel,” says hematologist Maria DeSancho of Weill Cornell Medical College. When damaged, the cells activate clotting.
- Other parts of the body’s response to C19 may be stoking clotting as well, each adding to the excess. “It’s a vicious cycle,” DeSancho says.
- When extensive clotting happens in C19 patients, it increases the chance they’ll die. A study of 184 patients admitted to the intensive care units of three hospitals in the Netherlands found that 75 had thromboses, clots that partially or completely block vessels; of those, 65 were pulmonary embolisms. As of April 22, 41 of the patients had died. The patients diagnosed with thromboses had a much higher risk of death than those without thromboses, researchers report in the July issue of Thrombosis Research.
- Although medicines are widely available to treat and prevent blood clots, the question is whether there’s a dose that will work for the dramatic amount of C19 clotting. Trials in the United States, Canada and Europe have begun recruiting patients to find the answer, with more trials in the planning stages.
- One trial, called RAPID COVID COAG, is enrolling hospitalized patients with confirmed C19 and with blood tests showing an elevated level of a substance called D-dimer, a by-product of blood clotting. (D-dimer can mean that a person has had a blood clot, or that the body is inflamed and at risk of a clot.)
- Participants will be randomly split into two groups. One will receive a low dose of an anticoagulant, one normally used to prevent a clot from forming in a person at risk due to surgery, for example. The other group will get a high dose, an amount normally used to break up a diagnosed blood clot.
- “The idea behind our trial is to initiate anticoagulation at a higher dose earlier on to determine whether or not that’s effective at decreasing the risk” of worsening illness or death, says hematologist Michelle Sholzberg of the University of Toronto and St. Michael’s Hospital in Toronto. The trial should wrap up by the end of the year.
- Though it’s not surprising that severe inflammation can increase the risk of clotting, the “predisposition to clots or full-blown clotting” seen in C19 appears distinct, Sholzberg says. “This is … a level of thromboinflammation that we have not really witnessed before on such a large scale.”
1. CDC says C19 cases in U.S. may be 10 times higher than reported
The estimate comes from a nationwide look at antibody tests.
- The true number of Americans who’ve been infected with C19 may top 20 million, according to new estimates from the Centers for Disease Control and Prevention.
- “Our best estimate right now is that for every case that’s reported, there actually are 10 other infections,” CDC director Dr. Robert Redfield said on a call with reporters Thursday.
- The estimate comes from looking at blood samples across the country for the presence of antibodies to the virus. For every confirmed case of C19, 10 more people had antibodies, Redfield said.
- Currently, there are 2.3 million C19 cases reported in the U.S. The CDC’s new estimate pushes the actual number of coronavirus cases up to at least 23 million.
- “This virus causes so much asymptomatic infection,” Redfield said. “The traditional approach of looking for symptomatic illness and diagnosing it obviously underestimates the total amount of infections.”
- The estimation comes amid rises in cases across the Southeast and Western U.S.
- He urged Americans to be vigilant about behavior measures known to minimize spread of the coronavirus.
- “The most powerful tool that we have is social distancing,” Redfield said. That means maintaining a physical distance of at least six feet in public, wearing face coverings and ongoing hand-washing.
- “If you must go out into the community, being in contact with fewer people is better than many,” Redfield added.
2. What antibody tests tell us about C19
By Zania Stamataki, a senior lecturer and researcher in viral immunology at the University of Birmingham
- The sheer speed with which C19 spread across the world, coupled with the novel nature of the virus, has meant that scientists and technicians have been playing a game of catch-up. But our knowledge, though incomplete, is now much greater than it was at the start of the outbreak, and medical systems are better equipped to respond.
- Part of this means we’ve got better at testing for the disease – attempting to meet the demands of people who want to know if they are, or have been, infected. Dr Alex Richter leads the clinical immunology labs at the University of Birmingham, where I work, and her team has developed serology tests that detect antibodies to Sars-CoV-2. For the time being, laboratory tests such as theirs are more sensitive than commercial antibody kits. But an increasing number of the latter are becoming available around the world, many of them over the counter.
- As we go further down this road, it’s important that people understand what antibodies reveal about our immune response to C19, and how protective immunity works.
- Basically, antibodies to the coronavirus show that you have been infected, although people with other recent coronavirus infections (which includes some common colds) may have cross-reactive antibodies, giving false positives. Serology tests vary in accuracy, but are more effective than so-called polymerise chain reaction (PCR) tests, which detect the presence of the virus itself. One reason is that they rely less on the skill of the person doing the sampling: antibodies in the blood are easier to detect than virus particles in nose or throat swabs.
- Such tests provide useful information about the way an infection has spread through a population. Newly infected people are unlikely to have detectable antibodies during the first few days, but most develop them after one to three weeks. Knowing how many have become infected helps us estimate the percentage of severe cases and deaths more accurately, and this tells us more about just how dangerous the new pathogen might be.
- It also helps us identify high-risk groups, which can offer clues as to how the virus may be transmitted. Take Richter’s study, in which she tested 516 healthcare workers for C19 antibodies: 34% of housekeeping staff came back positive compared with only 15% of staff working in intensive care. Such insights can be used to shield vulnerable groups with protective interventions.
- Antibodies also offer hope for future protection – but we have yet to fully characterise what immune protection from C19 might consist of.
- There are two major types of “memory” immune responses – changes to the body that mean you are able to recall a previous threat in order to mount a rapid protective response on reinfection. The first is driven by B cells, which produce antibodies. Vaccine research aims to generate potent, long-lasting antibodies that can protect us for life, but this is not always achieved. When antibodies wane, booster vaccinations can help. When viruses evolve to escape detection, like the fast-mutating flu, a newly designed vaccine is needed to stop them in their tracks.
- The second cell type able to remember an infection is the T cell. T cells may be sufficient to control infection in the absence of antibodies, and act by organising immune defences (so-called “helper” T cells) or directly killing infected cells to restrict new virus production (cytotoxic T cells). T cell responses have been detected in most C19 patients, and first-in-human vaccine trials have reported potent T cell activation. It is possible that T cells’ memory of Sars-CoV-2 may last longer than antibodies, as is the case in other coronaviruses.
- Can you develop a T cell response without developing antibodies? That seems to be a possibility: a small study of patients and their families shows that an unexpected six out of eight family members who caught the virus at home had T cell responses but no detectable antibodies.
- Currently there isn’t an off-the-shelf test to measure our T cell responses, and they do not show up in antibody tests. But then even a positive antibody test, at this stage, doesn’t tell us all that much about protection. The duration of any potentially protective immunity remains to be determined. As with so much related to this pandemic, we will know more as the months pass, and people who have recovered either remain well, or succumb to the virus again.
- Perhaps of more practical importance right now is a study that followed up 37 asymptomatic people who had positive PCR tests. This showed they had detectable levels of the virus for longer than those who had symptoms. Asymptomatic people are therefore likely to be more contagious. We also know that pre-symptomatic people, those in the early days following infection with Sars-CoV-2, are also highly contagious. Because we are often not aware that we are infected, measures to ensure social distancing and face covering are crucial when it comes to protecting others.
- There is some good news on the horizon, though. The first data emerging from vaccine studies show that animals can be protected from the coronavirus infection, and people do develop hallmarks of protective immunity. This hints that immunological memory is possible. The only way to know for sure, though, is to measure what happens when vaccination volunteers become infected. Ironically, this will take longer in countries that have successfully controlled the virus and have few ongoing infections.
- As a viral immunologist, I see immunity in C19 as a puzzle that we have yet to solve. But every week, new publications add new pieces to the jigsaw. When vaccines become widely available, protection will be much easier to assess using serology and lab-based tests.
- Right now, antibody tests do not confirm protection – it is just too early to know the quantity and type that would be necessary for that. They are still important, however, in charting the virus’s progress through our care homes, hospitals, public transport systems and workplaces (even if they do underestimate those affected). It is therefore vital that people who have agreed to be tested and come back positive are not disadvantaged in any way compared to those whose status is unknown. Without this kind of infection surveillance, much of the hardship of lockdown will have been in vain.
I. The Road Back?
A model developed by ISGlobal shows that deconfinement must be gradual and that individual behavior is a key factor.
- Individual behavior has a significant effect on preventing a large second wave of C19 infections. In fact, maintaining social distancing and other interventions such as the use of face masks and hand hygiene could remove the need for future lockdowns, according to a modeling study performed by the Barcelona Institute for Global Health (ISGlobal), an institution supported by the “la Caixa” Foundation.
- The findings, published in Nature Human Behaviour, also show that, in countries that have not yet reached the peak of active cases, lockdowns must remain in place for at least 60 days and deconfinement must be gradual in order to decrease the risk of second waves.
- Several countries that initially imposed strict lockdown measures to limit the spread of the coronavirus are in the process of lifting them. However, how and when to ease the restrictions is a difficult decision — a delicate balance between the need to reactivate the economy and the risk of a second wave of infections that could overwhelm healthcare systems.
- “The problem is that assessing this risk is difficult, given the lack of reliable information on the actual number of people infected or the extent of immunity developed among the population,” explains Xavier Rodó, head of ISGlobal’s Climate and Health program. In this study, Rodó’s team present projections based on a model that divides the population into seven groups: susceptible, quarantined, exposed, infectious not detected, reported infectious and confined, recovered and death. It also allows to simulate both the degree of population confinement and the different post-confinement strategies.
- “Our model is different because it considers the return of confined people to the susceptible population to estimate the effect of deconfinement, and it includes people’s behaviors and risk perception as modulating factors,” explains Xavier Rodó. “This model can be particularly useful for countries where the peak of cases has not yet been reached, such as those in the Southern hemisphere. It would allow to evaluate control policies and minimize the number of cases and fatalities caused by the virus” explains co-author and ISGlobal researcher Leonardo López.
- The use of face masks, hand hygiene and ‘shelter in place’ mandates have already demonstrated benefits. The aim of this study was to quantitatively evaluate their relevance as containment strategies. The results clearly show that the length of the first confinement will affect the timing and magnitude of subsequent waves, and that gradual deconfinement strategies always result in a lower number of infections and deaths, when compared to a very fast deconfinement process.
- In Spain, where the deconfinement was fast for half of the population and gradual for the rest, individual behavior will be key for reducing or avoiding a second wave. “If we manage to reduce transmission rate by 30% through the use of face masks, hand hygiene, and social distancing, we can considerably reduce the magnitude of the next wave. Reducing transmission rate by 50% could avoid it completely,” says Rodó.
- The results show that, even in countries that do not have the resources to test and trace all cases and contacts, social empowerment through the use of masks, hand hygiene, and social distancing, is key to stopping viral transmission.
- Simulations also show that loss of immunity to the virus will have significant effects on the spacing between epidemic waves — if immunity has a long duration (one year instead of a few months), then the time between the epidemic waves will double.
- The model considered total lockdowns and used data available until May 25, but did not take into account a possible effect of temperatures on viral transmission.
J. Projections & Our (Possible) Future
1. As C19 cases peak, a virus once again takes advantage of human instinct
- The natural response to a disaster is to at first believe that it is not happening. The C19 pandemic, we are learning, is a disaster playing out in slow motion — when every moment is a little bit worse than one would expect.
- In the United States, the result is a grim sense of déjà vu.
- Researchers have learned a lot about the coronavirus since it emerged in China at the end of 2019. They have learned more about how it spreads, and how to test for it. They have learned that two drugs, remdesivir and dexamethasone, show some benefit in the sickest patients.
- But they have also learned that the virus takes advantage of human instinct. Its long course means that it is possible to believe that things aren’t going to get that bad — long after they are actually becoming catastrophic. And many experts fear — though they may not be able to say for certain — that the U.S. is nearing the point of catastrophe again.
- The virus “defies intuition,” said Caitlin Rivers, an assistant professor at the Johns Hopkins Bloomberg School of Public Health. “People like to see the impact of changes in the data much sooner than we actually observe.”
- In reality, it takes three weeks, sometimes even a month, for surges in the number of case counts to show up as increases in deaths, Rivers said.
- There are reasons to believe that things could be different in the states that currently are seeing surges, which include Texas, Florida, South Carolina, and Utah, than they were in New York. The people getting sick now seem younger, on average, which may mean that fewer get serious illness. Still, Rivers said, using the cold language of epidemiology: “It’s hard to imagine that this increase in incidence will not be reflected in any way in the number of deaths.”
- Remember, after all, how things played out in New York. The first confirmed case was announced on March 1. A little more than a week later, the National Guard was being called into the city of New Rochelle. At the end of the month, 76,000 New Yorkers had been diagnosed with Covid and more than 17,000 had died. Cases swelled to 390,000, and deaths 25,000 before the epidemic there came under control.
- “Even though I am a lifelong, serious optimist, I think Covid calls for realism,” said Susan Desmond-Hellmann, the former CEO of the Bill and Melinda Gates Foundation. “And so for me, this is a moment of realism and humans, including this human, love denial. We love denial.”
- The facts are the facts, Desmond-Hellmann said. An estimated 2.4 million Americans have been diagnosed, and more than 120,000 people have died of this novel coronavirus in the U.S. “The virus is still here,” she said.
- Rivers said what frustrates her is the sense of resignation about the current state of affairs — to “explain why it can’t be helped and that this is just the way that things are destined to unfold, when the fact is there’s a lot that we could do.”
- “There are many other countries that have gained control of their outbreak and they are in a much better place than we are,” she noted.
- New Zealand and Iceland, the best examples, are islands. But the list includes much of Europe. Italy, Spain, and Germany have controlled their outbreaks, even after being hit hard. The solutions are the same simple ones public health experts have recommended from the beginning: further ramping up the availability and speed of testing, so patients know when they are infected. Isolating people when they are sick so they don’t infect others. Avoiding crowds and close contact with other people. Washing hands frequently. And, most experts now agree that face masks reduce transmission, helping to keep the virus in check.
- “Opening up doesn’t mean stop wearing a mask,” said Desmond-Hellmann. “Opening up means the opposite.”
- And returning to some parts of normal life, she said, would just not be sensible. “I’m very pro-religion,” Desmond-Hellmann said. “I think religion is very important for people. But do you really want to put people together and sing hymns right now?”
- Both Desmond-Hellmann and Rivers said they were frustrated that the simple message of public health has been politicized: Until there is an effective vaccine, we need to use the measures we have — masks, some distancing, and reasonable steps to reduce infection — to try to keep the virus in check.
- “I would love for everyone from President Trump to the governor of every state, to the mayors to people in leadership roles to make it a cultural norm, to make it popular, fun, fashionable to wear a face mask,” Desmond-Hellmann said. “Because it’s all we’ve got right now.”
K. Practical Tips & Other Useful Information
1. What To Look For In A Face Mask, According To Science
- In a matter of weeks, face masks went from being considered unnecessary, and possibly harmful, to mandatory in many places across the U.S. You’re forgiven if you’ve got a bit of whiplash.
- Currently, the scientific consensus is that face masks are at least somewhat effective at preventing the spread of C19, and both the World Health Organization and the Centers for Disease Control and Prevention recommend wearing a cloth face covering. But which mask should you choose? Is the hand-stitched one your father-in-law made just as good as the one produced by your favorite fashion retailer? Are disposable surgical masks just as good? How many layers of fabric should it have?
- To help you wade through the mountain of options, we’ve taken a look at the (admittedly limited) science available and spoken to experts to create a science-backed guide to mask shopping.
Do I need to wear a mask?
- Unless you’re under the age of 2, have a specific medical condition that makes it hard for you to wear a mask, or are able to keep six feet away from other people at all times (hello, hermits!), you should wear a mask whenever you leave your house, according to current recommendations from the CDC, WHO and public health experts. And it may be a requirement in your city or state.
What does a mask do?
- We now know that the main way the novel coronavirus is spread is through respiratory droplets: tiny bits of spit and other materials that are expelled from your mouth and nose when you sneeze, cough, talk or breathe. If you’re carrying the virus, it can hitch a ride on these droplets and spread to surfaces or to other people — entering their nose or mouth and causing infection. A mask can physically block these droplets from travelling further than your face. While they can also provide some protection against C19, there are lots of ways to come into contact with infectious droplets (touching a surface where droplets have landed, or having droplets land on your eyes or skin), but fewer ways of spreading droplets (likely only through your mouth and nose). Because of this, masks do a much better job at preventing an infectious person from spreading the disease than they do of protecting a healthy person from catching it. Wearing a mask is about not spreading the virus yourself rather than providing protection for you.
- “You wear one to protect me and I wear one to protect you,” said Dr. Scott Segal, an anesthesiologist at Wake Forest Baptist Health in North Carolina who has run lab tests of face mask materials.
Should I go disposable or reusable?
- In lab tests, disposable surgical masks perform well for both breathability and blocking respiratory droplets. Depending on the material, both kinds of masks can be equally effective and safe. But disposable masks are really only designed to be worn once then thrown away (they start to break down and become less effective after wearing), which isn’t great from an environmental perspective. Already, piles of single use personal protective equipment have been washing up on shorelines. If a disposable mask is the only option, wear it, but a reusable, washable mask is a better long-term solution.
What material is best for a reusable face mask?
- A lot of scientists have been trying to figure this out, and the answer isn’t exactly straightforward (is anything straightforward when it comes to COVID?). Different researchers have set up devices that spray tiny droplets at fabric and then measured how much of it comes through the other side, while also measuring air flow to determine breathability. What they’ve found is that it’s less about the type of fabric — cotton, linen, silk — and more about the quality of fabric, according to Segal. Higher quality fabrics have a tighter weave and thicker thread that do a better job of blocking droplets from passing through.
- But you also want the fabric to be breathable, according to Taher Saif, a mechanical engineer at the University of Illinois who has been researching face mask material. Saif said if breath can’t get through the mask, it will find another way out, allowing respiratory droplets to spread.
- “Imagine you take aluminum foil and make a mask out of it,” Saif said. “All the air will be forced out the sides. If you sneeze or cough, the majority of the droplets will escape out the side and you lose the point of the mask.”
- So you should be able to comfortably breathe through the mask. But measuring exactly how effective a specific fabric is at blocking droplets requires a lab, and just because one lab finds a mask made from a 100 percent cotton T-shirt to be effective doesn’t mean the cotton T-shirt you have in your drawer is the same material. In lieu of more precise measurements, Segal offered a rule of thumb: hold the material up to a bright light.
- “Look at the light coming through the fabric,” Segal said. “If it outlines individual fibers and you can see the light through fabric, it’s probably not as effective. The less of that you can see, the better the filter.”
How many layers are best?
- According to research that has been published or prepublished so far, two layers do a better job than one, and three layers do a better job than two.
- In its guidelines, the WHO recommends a minimum of three layers, and many major manufacturers seem to be using this as a rule of thumb. So why not go four layers? You could, but remember you don’t want to sacrifice breathability (see above). Still, choosing a mask with more layers will generally add more protection.
Does thread count matter?
- Thread count refers to the number of threads per square inch of fabric, but more isn’t necessarily better, according to Segal.
- “Satin sheets have super high thread count but you can hardly breathe through them because it’s so tight,” Segal said. “That may have to do not just with thread count but also tightness of weave.”
What style should I buy?
- The most effective masks are ones that cover both your nose and mouth and form a somewhat snug seal at the edges of the mask. Without a professional grade mask like an N95 respirator, you’re not going to get an airtight seal, but that’s okay — we’re aiming for good enough, not perfect. For everyday use, the experts I spoke to said a comfortable but snug mask does the trick.
Should I buy handmade or mass produced?
- The efficacy of the mask has more to do with the material than whether it was made in a factory or at your kitchen table. Even homemade, no-sew, T-shirt masks have performed well in lab tests, especially when made with multiple layers. Check out the material and choose (or make) the mask you find most comfortable and will be likely to wear.
What about those exhalation vents?
- Exhalation vents were designed for masks that serve a very different purpose than the ones we should be wearing now. Those masks are meant to prevent the wearer from inhaling particles, not to block them from exhaling particles, so the vents make it easier to breathe while still stopping the bad stuff from getting in. With C19, masks are meant to block your respiratory particles from getting out, not to block other things from getting in, so an exhalation vent defeats the purpose of the mask.
What if I pick the wrong one?
- At the end of the day, many experts also say that any face covering is better than no face covering. Do your best to find a mask that is breathable and that you don’t mind wearing, and you should be in good shape.
- To drive the point home, Saif held up a Kleenex during our video interview and said: “Even this would be better than nothing.”
L. Links to Other Scientific Findings & Research
- COVID-19: Bacteriophage could decrease mortality
- Bacterial predator could help reduce COVID-19 deaths
- Those with Intellectual & Developmental Disabilities living in group homes more likely to die from COVID-19
- The Lancet Child & Adolescent Health: First Europe-wide study of children confirms COVID-19 predominately causes mild disease in children and fatalities are very rare
- Hospitals improvise to address COVID-19 PPE shortage
- Researchers identify N95 respirator decontamination method using microwave-generated steam
- MSK researchers find that common cancer treatments don’t worsen coronavirus infection
- Far-UVC light safely kills airborne coronaviruses
- Researchers develop low-cost, easy-to-use emergency ventilator for COVID-19 patients