Recent Developments & Information
August 4, 2020
Without reliable information, we rely on fear or luck.
“A number of vaccines are now in phase three clinical trials and we all hope to have a number of effective vaccines that can help prevent people from infection. However, there’s no silver bullet at the moment and there might never be.”Dr. Tedros, Director General of World Health Organization
“The only way we’re really going to have a real robust economic recovery and save American lives from COVID-19 is to fully lock down the entire nation and all of its inhabitants. Otherwise, we’re going to have flare-ups, lockdowns, and a very halting recovery with many more job losses and many more bankruptcies for an extended period of time, unfortunately.”Neel Kashkari, Minneapolis Federal Reserve President
“In our opinion, re-imposing city lockdowns at this stage might be not be the ideal solution to control infection, from a cost/ benefit perspective, especially for developed countries. Even for developing countries, an overall cost-benefit analysis indicates that, in a potentially bigger second wave, lockdowns may not be the ideal approach.”JPMorgan
A. The Pandemic As Seen Through Headlines
B. Numbers & Trends
1. Cases & Tests
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity (8/3)
C. New Scientific Findings & Research
D. Vaccines & Testing
E. Improved & Potential Treatments
F. Concerns & Unknowns
G. The Road Back?
H. Back To School!?
I. Projections & Our (Possible) Future
J. Johns Hopkins COVID-19 Update (8/3)
A. The Pandemic As Seen Through Headlines
(In no particular order)
- World faces ‘generational catastrophe’ if school closures continue, U.N. chief warns
- US reports smallest daily coronavirus cases increase in almost 4 weeks
- Cases are climbing in Midwest states with previously low infections
- 4 former FDA commissioners: Blood plasma might be the covid-19 treatment we need
- Latin America exceeds 5 million COVID-19 cases
- CDC releases back-to-school decision-making tool for parents
- Former FDA Commissioner Gottlieb says lockdowns may not always be most appropriate solution
- Dr. Birx says U.S. has entered a ‘new phase’ of pandemic as cases, deaths rise
- NY hits record new low for coronavirus hospitalizations
- CA Gov. Newsom says all major COVID-19 benchmarks in the state are trending down
- NJ lowers limit on number of people allowed at indoor, outdoor gatherings
- Arizona reports just 1,030 new cases as hospitalizations fall for 12th day
- New Florida cases decline as testing stations closed
- 46 hospitals in FLA have no open ICU beds
- Maine hospital sees coronavirus resurgence after state visitors report positive tests
- San Francisco flattened the curve early. Now, coronavirus cases are surging.
- More schools reopen in Indiana, Georgia, elsewhere
- Georgia’s largest school district reportedly sees surge of employees exposed to COVID-19
- Maryland Gov. Hogan curtails power of local health officers to order blanket school closures
- Parents struggle as schools reopen amid coronavirus surge
- 4 in 5 Parents Considering Homeschooling Kids This Fall
- Teachers protest across U.S. over re-opening schools in pandemic
- Houston mayor asks police to issue tickets to people who aren’t masked
- If Congress can’t pass this coronavirus legislation, is the institution broken?
- CEOs to Congress: A lot more small businesses will fail without new aid
- Congress flails as coronavirus ravages the nation and the economy stalls
- President Trump says he’s examining executive orders on evictions, payroll taxes if he can’t reach deal with Democrats
- UK gov’t games out plan to close London should ‘second wave’ intensify
- Iran’s death toll is 3x larger than previously believed
- One person is dying of coronavirus every seven minutes in Iran
- Australian state (Victoria) imposes strict lockdown measures after declaring state of disaster
- Philippines President Duterte revives Manilla lockdown
- Hong Kong reports 80 new cases, first reading below 100 cases in two weeks
- Bahamas cases surge after international visitors allowed back, new lockdown declared
- Spain’s new wave of infections hits young, middle aged
- Israel to Draft Reservists to Help Fight Coronavirus Outbreak
- a coronavirus vaccine in record time is hard. Distributing it to tens of millions may be equally daunting.
- Coronavirus vaccine will not change world right away
- Do Investors Know They Are Skiing In An Avalanche Zone?
- US New Vehicle Sales Are Expected To Keep Rebounding In July Despite Virus Resurgence
- Macau’s Gaming Revenues Crash 94.5% In July As Recovery Hopes Dim
- One Of The First Ships To Resume Cruising Is Having A COVID Outbreak
- Sports teams experiment with facial recognition for contactless admission
- Coronavirus unknowns may mean billions in healthcare costs still ahead
- 83% of NYC restaurants, bars unable to pay full rent
- Singapore will make travelers wear electronic tags to enforce quarantine
- Owners of NYC riverboat busted for hosting more than 170 people
- Wild brawl erupts on flight after passengers refuse to wear masks
- New York City’s socially-distanced dining experiment will return next year, with or without virus
- Big 12 sets football schedule of nine conference games, one nonconference matchup
- Major League Soccer close to finalizing plans to resume season
- Baseball must learn from these outbreaks, or its teetering season is doomed
- The University of Texas at Austin has banned both on and off-campus parties for the fall semester, though it’s unclear how those rules will be enforced
- With coronavirus cases reported at some reopened schools, protesters take to the streets with fake coffins
- Las Vegas gambler removed from famous 4 Queen casino in handcuffs after he went in without wearing a mask
- Hundreds gather In Illinois without masks for annual ‘White Trash Bash’ boat event
- Coronavirus-sniffing dogs dispatched at Dubai Airport
- Advice from a woman who survived covid-19, the 1918 flu – and cancer
- The Internet wants to keep you ‘doom-scrolling.’ Here’s how to break free
- Should asking a stranger to take your photo go the way of the daguerreotype?
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 = 18,435,432 (+1.1%)
- New Cases = 199,861 (-24,606) (+11.0%)
- New Cases (7 day average) = 256,760 (-2,672) (-1.0%)
- Number of new cases has declined by approx. 90,000 in last 4 days
- Number of new cases has declined for 4 consecutive days
- 7 day average of new cases has declined for 4 consecutive days (most consecutive days of decline since the beginning of the pandemic)
- 1,000,000+ cases every 4 days (based on 7 day average)
US Cases & Testing:
- Total Cases = 4,862,174 (+1.0%)
- New Cases = 48,622 (-940) (-1.9%)
- Percentage of New Global Cases = 24.3%
- New Cases (7 day average) = 60,953 (-1,879) (-3.0%)
- Total Number of Tests = 60,937,541
- Percentage of positive tests (7 day average) = 7.9%
- Number of new cases has declined 22,453 during the last 4 days
- Number of new cases has declined 3 consecutive days
- Number of new cases is 13,148 less than one week ago
- Number of new cases in US fall to 2nd highest, behind India
- 7 day average of cases has declined for 8 consecutive days
- 7 day average of the percentage of positive tests continues to decline
- Total Deaths = 696,823 (+0.6%)
- New Deaths = 4,372 (-8) (-0.2%)
- New Deaths (7 day average) = 5,699 (+25) (+0.4%)
- Number of new deaths has declined 2,626 over last 6 days
- Number of new deaths has declined for 5 consecutive days
- 7 day average of new deaths has moved up and down within a narrow range since 7/26
- Total Deaths = 158,929 (+0.4%)
- New Deaths = 568 (+101) (+21.6%)
- Percentage of Global New Deaths = 13.0%
- New Deaths (7 day average) = 1,125 (-4) (-0.4%)
- Number of new deaths is 29 less than last week
- Number of new deaths in US fall to 3rd highest, behind India and Brazil
- 7 day average of new deaths declined for the first times since recent rise in daily deaths began on 7/5, which may indicate that the rise in daily deaths has peaked
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity (8/3)
Source: Worldometer and The Covid Tracking Project
C. New Scientific Findings & Research
- One of the immune system’s oldest branches, called complement, may be influencing the severity of C19 disease, according to a new study from researchers at Columbia University Irving Medical Center.
- Among other findings linking complement to COVID, the researchers found that people with age-related macular degeneration — a disorder caused by overactive complement — are at greater risk of developing severe complications and dying from COVID.
- The connection with complement suggests that existing drugs that inhibit the complement system could help treat patients with severe disease.
- The study was published today (August 3, 2020) in Nature Medicine.
- The authors also found evidence that clotting activity is linked to COVID severity and that mutations in certain complement and coagulation genes are associated with hospitalization of COVID patients.
- “Together these results provide important insights into the pathophysiology of C19 and paint a picture for the role of complement and coagulation pathways in determining clinical outcomes of patients infected with SARS-CoV-2,” says Sagi Shapira, PhD, MPH, who led the study with Nicholas Tatonetti, PhD, both professors at Columbia University Vagelos College of Physicians and Surgeons.
Findings Stem from Study of Coronavirus Mimicry
- The idea to investigate the role of coagulation and complement in COVID began with a sweeping survey of viral mimicry across all viruses on earth — over 7,000 in all.
- “Viruses have proteins that can mimic certain host proteins to trick the host’s cells into aiding the virus with completing its life cycle,” Shapira says. “Beyond the fundamental biological questions that we were interested in addressing, based on our previous work and the work of others, we suspected that identifying those mimics could provide clues about how viruses cause disease.”
- Coronaviruses, the survey found, are masters of mimicry, particularly with proteins involved in coagulation and proteins that make up complement, one of the oldest branches of the human immune system.
- Complement proteins work a bit like antibodies and help eliminate pathogens by sticking to viruses and bacteria and marking them for destruction.
- Complement can also increase coagulation and inflammation in the body. “Unchecked, these systems can also be quite detrimental,” says Shapira.
- “The new coronavirus — by mimicking complement or coagulation proteins — might drive both systems into a hyperactive state.”
Macular Degeneration Associated with Greater COVID Mortality
- If complement and coagulation influence severity of COVID, people with pre-existing hyperactive complement or coagulation disorders should be more susceptible to the virus.
- That led Shapira and Tatonetti to look at COVID patients with macular degeneration, an eye disease caused by overactive complement, as well as common coagulation disorders like thrombosis and hemorrhage.
- Among 11,000 C19 patients who came to Columbia University Irving Medical Center with suspected C19, the researchers found that over 25% of those with age-related macular degeneration died, compared to the average mortality rate of 8.5%, and roughly 20% required intubation. The greater mortality and intubation rates could not be explained by differences in the age or sex of the patients.
- “Complement is also more active in obesity and diabetes,” Shapira says, “and may help explain, at least in part, why people with those conditions also have a greater mortality risk from COVID.”
- People with a history of coagulation disorders also were at increased risk of dying from COVID infection.
Coagulation and Complement Pathways Activated
- The researchers then examined how gene activity differed in people infected with the coronavirus.
- That analysis revealed a signature in COVID-infected patients indicating that the virus engages and induces robust activation of the body’s complement and coagulation systems.
- “We found that complement is one of the most differentially expressed pathways in SARS-CoV-2 infected patients,” Tatonetti says. “As part of the immune system, you would expect to see complement activated, but it seems over and above what you’d see in other infections like the flu.”
Some Coagulation and Complement Genes are Associated with Hospitalization
- More evidence linking severe COVID with coagulation and complement comes from a genetic analysis of thousands of COVID patients from the U.K. Biobank, which contains medical records and genetic data on half a million people.
- The authors found that variants of several genes that influence complement or coagulation activity are associated with more severe COVID symptoms that required hospitalization.
- “These variants are not necessarily going to determine someone’s outcome,” Shapira says. “But this finding is another line of evidence that complement and coagulation pathways participate in the morbidity and mortality associated with C19.”
Targeting Coagulation and Complement
- Physicians treating C19 patients have noticed coagulation issues since the beginning of the pandemic, and several clinical trials are underway to determine the best way to use existing anti-coagulation treatments.
- Complement inhibitors are currently used in relatively rare diseases, but at least one clinical trial is testing the idea with COVID patients.
- “I think our findings provide a stronger foundation for the idea that coagulation and complement play a role in COVID,” Tatonetti says, “and will hopefully inspire others to evaluate this hypothesis and see if it’s something that can be useful for fighting the ongoing pandemic.”
2. Transferrin identified as potential contributor to C19 severity
- The University of Kent’s School of Biosciences and the Institute of Medical Virology at Goethe-University, Frankfurt am Main, have identified that a glycoprotein known as transferrin may critically contribute to severe forms of C19.
- It is currently not known why some individuals develop only mild or no symptoms when infected, whilst others experience severe, life-threatening forms of the disease. However, it is known that the risk of C19 becoming severe increases with age and is higher in males than in females. Many severe C19 cases are characterized by increased blood clotting and thrombosis formation.
- The team combined existing data on gene expression in humans and infected cells to search for molecules involved in blood coagulation that differ between females and males, change with age, and are regulated in response to C19 infection.
- Out of more than 200 candidate factors, researchers identified a glycoprotein called transferrin to be a procoagulant (a cause of blood clotting) that increases with age, is higher in males than in females, and is higher in coronavirus-infected cells. Hence, transferrin may have potential as a biomarker for the early identification of C19 patients at high risk of severe disease.
- Katie-May McLaughlin, the first author of the study said: ‘It is very exciting to be involved in such an important study that may improve therapies for C19 in its most severe form’.
3. Common cold antibodies fail to neutralize C19
- Researchers in Austria have shown that antibodies with potent neutralizing activity against a well-established seasonal coronavirus had no neutralizing activity against the coronavirus.
- The team carried out the study to test whether the coronavirus could potentially be neutralized by antibodies induced by seasonal coronaviruses that are already circulating.
- The analysis of intravenous immunoglobulin (IVIG) lots produced against human coronavirus (hCoV) 299E, a long-recognized cause of the common cold, showed high titers of neutralizing antibodies (nAbs) against the 299E virus, but no cross-neutralization effect against the coronavirus.
- Thomas Kreil and colleagues from Baxter AG, Vienna, say the finding suggests that nAbs against well-known seasonal coronaviruses cannot neutralize the coronaviru and that the currently available IVIG lots would not offer any protection against the virus.
- A pre-print version of the paper can be accessed on the server bioRxiv (here), while the article undergoes peer review.
- The coronavirus belongs to the same family of coronaviruses that includes strains currently circulating seasonally as respiratory viruses.
- The thousands of plasma donations previously made by people exposed to such viruses can be pooled to produce IVIG lots containing various antibodies generated against the infectious agents.
- These IVIG lots can be used to protect immunocompromised individuals, for example, against circulating viral infections.
- Following the emergence of a new virus, detectable levels of antibodies only occur in IVIG lots once a certain proportion of donors have contracted and recovered from the infection. Furthermore, for the lots to offer any protective, neutralizing effect, an even higher proportion of recovered donors is needed.
- The coronavirus belongs to the Coronaviridae family, which includes the hCoVs 229E, NL63, OC43, and HKU1. These agents generally cause a self-limiting and mild illness, although they can also lead to more severe conditions such as pneumonia.
- Given the long-term circulation of these hCoVs, by time plasma was pooled from thousands of donors, the IVIG lots contained significant levels of nAbs. However, whether these may cross-react or potentially even neutralize the novel and related coronavirus remains unclear.
- Some antibody binding assays have demonstrated a certain degree of cross-reactivity, but the more clinically relevant functional neutralization assays have detected no or only minimal levels of cross-neutralization.
The question is of significant clinical relevance to people with immunodeficiencies
- Kreil and colleagues say the question is of particular clinical relevance for people with immune deficiencies (PIDs) since their health depends on whether they can be treated with immunoglobulin preparations that contain neutralizing antibodies against the various pathogens surrounding them.
- “Coronavirus cross-neutralizing antibodies in IVIGs, if they were present, might afford some protection to PIDs, and may even represent a treatment option for C19 patients,” writes the team.
- Now, the researchers have tested IVIG lots produced from plasma collected in Europe and the US for nAbs against coronavirus and the longer circulating hCoV-299E to gauge whether antibodies against existing seasonal coronaviruses might cross-neutralize coronavirus.
- The analysis showed that the IVIG lots contained high titers of nAbs against hCoV-229E. However, testing the same IVGF lots using a highly specific coronavirus neutralization assay showed no cross-neutralization.
- “The finding confirms that the existing hCoV-229E-specific nAbs, as well as the presumably present nAbs against the other seasonal hCoVs, have no cross-neutralizing capacity to the coronavirus,” writes the team.
- The researchers say another study testing 21 IVIG lots using the coronavirus specific ELISA assay that had previously correlated with a neutralization test, also did not detect the presence of any cross-reacting antibodies.
- This, together with the current study, shows that “two experimentally robust studies have not found coronavirus nAbs in IVIG lots produced from pre-pandemic plasma,” they write.
- Therefore, “currently available IVIGs cannot be expected to afford protection from coronavirus infection,” concludes the team.
4. Scientists Identify Possible “Achilles’ Heel” of Coronavirus
- In the case of an infection, the coronavirus must overcome various defense mechanisms of the human body, including its non-specific or innate immune defense. During this process, infected body cells release messenger substances known as type 1 interferons. These attract natural killer cells, which kill the infected cells.
- One of the reasons the coronavirus is so successful — and thus dangerous — is that it can suppress the non-specific immune response. In addition, it lets the human cell produce the viral protein PLpro (papain-like protease). PLpro has two functions: It plays a role in the maturation and release of new viral particles, and it suppresses the development of type 1 interferons. The German and Dutch researchers have now been able to monitor these processes in cell culture experiments. Moreover, if they blocked PLpro, virus production was inhibited and the innate immune response of the human cells was strengthened at the same time.
- Professor Ivan Dikic, Director of the Institute of Biochemistry II at University Hospital Frankfurt and last author of the paper, explains: “We used the compound GRL-0617, a non-covalent inhibitor of PLpro, and examined its mode of action very closely in terms of biochemistry, structure and function. We concluded that inhibiting PLpro is a very promising double-hit therapeutic strategy against C19. The further development of PLpro-inhibiting substance classes for use in clinical trials is now a key challenge for this therapeutic approach.”
- Another important finding from this work is that the viral protein PLpro of coronavirus cleaves off ISG-15 (interferon-stimulated gene 15) from cellular proteins with a higher level of activity than the SARS equivalent, which leads to greater inhibition of type I interferon production. This is concordant with recent clinical observations which show that C19 exhibits a reduced interferon response in comparison to other respiratory viruses such as influenza and SARS.
- To understand in detail how inhibiting PLpro stops the virus, researchers in Frankfurt, Munich, Mainz, Freiburg, and Leiden have worked closely together and pooled their biochemical, structural, IT and virological expertise.
- Donghyuk Shin, postdoctoral researcher and first author of the paper, says: “Personally, I would like to underline the significance of science and research and in particular emphasize the potential generated by a culture of collaboration. When I saw our joint results, I was immensely grateful for being a researcher.”
- Professor Sandra Ciesek, Director of the Institute of Medical Virology at University Hospital Frankfurt, explains that the papain-like protease is an extremely attractive anti-viral goal for her as a physician because its inhibition would be a “double strike” against the coronavirus. She highlights the excellent collaboration between the two institutes: “Especially when investigating a new clinical picture, everyone profits from interdisciplinary collaboration as well as different experiences and viewpoints.”
- Read the Nature study here: Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity
5. Lung Ultrasound Reveals Duration and Severity of C19
- According to an open-access article published in ARRS’ American Journal of Roentgenology (AJR), lung ultrasound (US) was highly sensitive for detecting abnormalities in patients with coronavirus disease (C19), with B-lines, a thickened pleural line, and pulmonary consolidation the most commonly observed features.
- “In addition,” concluded Yao Zhang of at China’s Beijing Ditan Hospital, “our results indicate that lung US findings can be used to reflect both the infection duration and disease severity.”
- Lung ultrasound image obtained with linear probe. Multiple confluent B-lines (arrows) and patchy pulmonary consolidation (asterisk) are visualized. Credit: American Journal of Roentgenology (AJR)
- From March 3 to March 30, 2020, Zhang and colleagues performed lung US on consecutive patients with positive reverse transcriptase polymerase chain reaction (RTPCR) test results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the Fisher exact test to compare the percentages of patients with each US finding between groups with different symptom durations and disease severity.
- All 28 patients (14 men and 14 women; age range, 21–92 years) had positive findings on both lung US and chest CT. On US, B-lines were present in 100% of patients, and 19 (67.9%) patients had pulmonary consolidation. Thickened pleural lines were observed in 17 patients (60.7%), and only one patient (3.6%) showed a small amount of pleural effusion.
- Chest CT image shows reticular and interlobular septal thickening and patchy, focal opacities associated with architectural distortion. This patient was classified in critical group and was assigned to severe group for statistical analysis. Credit: American Journal of Roentgenology (AJR)
- “A thickened pleural line was more frequently observed on US in patients with longer time intervals after the initial onset of symptoms,” Zhang et al. noted, adding that pulmonary consolidations—visualized as tissuelike hypoechoic regions, reflecting highly reduced air flow and increased quantity of inflammatory cellular exudate—were more common in severe and critical cases.
- Acknowledging that portable radiography could be just as useful in evaluating consolidation, “a bedside portable, handheld US system or even a robot-assisted tele-US system (a unique technique for physicians to remotely scan patients) further minimizes the number of health care workers and medical devices exposed to C19,” wrote Zhang and team.
- The authors of this AJR article also proposed that severity scoring for lung US, similar to CT severity scores, should be developed to facilitate more accurate comparisons in future studies.
6. Six strains of the coronavirus
- The coronavirus presents at least six strains. Despite its mutations, the virus shows little variability, and this is good news for the researchers working on a viable vaccine.
- These are the results of the most extensive study ever carried out on coronavirus sequencing. Researchers at the University of Bologna drew from the analysis of 48,635 coronavirus genomes, which were isolated by researchers in labs all over the world. This study was published in the journal Frontiers in Microbiology. It was then possible for researchers to map the spread and the mutations of the virus during its journey to all continents.
- The first results are encouraging. The coronavirus presents little variability, approximately seven mutations per sample. Common influenza has a variability rate that is more than double.
- “The SARS-CoV-2 coronavirus is presumably already optimized to affect human beings, and this explains its low evolutionary change”, explains Federico Giorgi, a researcher at Unibo and coordinator of the study. “This means that the treatments we are developing, including a vaccine, might be effective against all the virus strains”.
- Currently, there are 6 strains of coronavirus. The original one is the L strain, that appeared in Wuhan in December 2019. Its first mutation – the S strain – appeared at the beginning of 2020, while, since mid-January 2020, we have had strains V and G. To date strain G is the most widespread: it mutated into strains GR and GH at the end of February 2020.
- “Strain G and its related strains GR and GH are by far the most widespread, representing 74% of all gene sequences we analyzed”, says Giorgi. “They present four mutations, two of which are able to change the sequence of the RNA polymerase and Spike proteins of the virus. This characteristic probably facilitates the spread of the virus”.
- If we look at the coronavirus map, we can see that strains G and GR are the most frequent across Europe and Italy. According to the available data, GH strain seems close to non-existence in Italy, while it occurs more frequently in France and Germany. This seems to confirm the effectiveness of last months’ containment methods.
- In North America, the most widespread strain is GH, while in South America we find the GR strain more frequently. In Asia, where the Wuhan L strain initially appeared, the spread of strains G, GH and GR is increasing. These strains landed in Asia only at the beginning of March, more than a month after their spread in Europe.
- Globally, strains G, GH and GR are constantly increasing. Strain S can be found in some restricted areas in the US and Spain. The L and V strains are gradually disappearing.
- Besides these 6 main coronavirus strains, researchers identified some infrequent mutations, that, at the moment, are not worrying but should nevertheless be monitored.
- “Rare genomic mutations are less than 1% of all sequenced genomes”, confirms Giorgi. “However, it is fundamental that we study and analyze them so that we can identify their function and monitor their spread. All countries should contribute to the cause by giving access to data about the virus genome sequences”.
Source: The six strains of SARS-CoV-2
D. Vaccines & Testing
1. C19 Vaccine Innovation Could Massively Speed Up Worldwide Production
- Responding to a need to quickly develop billions of doses of lifesaving C19 vaccines, a scientific team at The University of Texas at Austin has successfully redesigned a key protein from the coronavirus, and the modification could enable much faster and more stable production of vaccines worldwide. The new findings are described in the journal Science.
- Most coronavirus vaccine candidates train the human immune system to recognize a key protein on the surface of the coronavirus called the spike protein in order to fight infection.
- Researchers designed a new version of this protein that, when expressed in cells, produces up to 10 times more protein than that of an earlier synthetic spike protein already in use in multiple C19 vaccines. Along with colleagues at the National Institutes of Health, several members of the UT research team also designed the earlier version of the spike protein found in at least two C19 vaccine candidates currently in U.S. clinical trials.
- “Depending on the type of vaccine, this improved version of the protein could reduce the size of each dose or speed up vaccine production,” said Jason McLellan, an associate professor in the Department of Molecular Biosciences and senior author of the paper. “Either way, it could mean more patients have access to vaccines faster.”
- Dubbed HexaPro, the new protein is also more stable than the team’s earlier version of the spike protein, which should make it easier to store and transport. It also keeps its shape even under heat stress, during storage at room temperature and through multiple freeze-thaws. Such qualities are desirable in a robust vaccine.
- The Bill & Melinda Gates Foundation has contributed to the development of the technology through a grant in the interest of making vaccines accessible to people in lower-income countries. Vaccine companies with different platform technologies will have the ability to test and further develop COVID vaccines that use HexaPro. McLellan has also indicated there is interest from partners in extending access to the technology to people in the developing world.
- “Four billion people living in developing countries will need access to a vaccine, as all of us will,” McLellan said.
- Jason S. McLellan, associate professor of molecular biosciences, left, and graduate student Daniel Wrapp, right, work in the McLellan Lab at The University of Texas at Austin Monday February 17, 2020. Credit: Vivian Abagiu/University of Texas at Austin
- HexaPro also could be used in C19 antibody tests where it would act as a probe to identify the presence of antibodies in a patient’s blood, indicating whether a person has previously been infected with the virus.
- The paper’s first author is Ching-Lin Hsieh, a postdoctoral researcher in McLellan’s lab. Corresponding authors are McLellan; Ilya Finkelstein, an associate professor in the Department of Molecular Biosciences; and Jennifer Maynard, a professor in the Cockrell School of Engineering.
- The team’s original version of the spike protein forms the basis of vaccine candidates currently in human clinical trials, including Moderna’s mRNA-1273 and Novavax’s NVX-CoV2373.
- For nucleic acid-based vaccines that use the patient’s own cells to create the viral proteins that trigger an immune response, such as mRNA-1273, this improved spike protein might enable next-generation versions that require a much smaller dose to elicit the same immune response from a patient. For subunit vaccines that contain a version of the actual viral protein as an antigen, such as NVX-CoV2373, many more vaccine doses could be produced in the same time frame. Either way, from a production standpoint, this could mean accelerating access to lifesaving vaccines.
- Drawing on their experience creating stabilized proteins as vaccines against MERS-CoV, the coronavirus that causes Middle East respiratory syndrome, and other viruses, the researchers identified 100 different modifications to the spike protein that they believed might lead to a more stable, more highly expressed version. Next they created 100 different versions of the protein by inserting the genetic blueprints for each version into a different culture of human cells. Of those 100 versions of the spike protein, 26 were more stable or had higher expression.
- The researchers then took four of those beneficial modifications, plus two from their original stabilized spike protein, and combined them to create HexaPro. When they inserted the genetic blueprints for this version of the spike protein into a human cell culture, the cells produced 10 times as much protein than that of their original protein.
- Biotechnology company Sino Biological has obtained a non-exclusive license from UT Austin to manufacture HexaPro and sell it to researchers around the world.
2. New 90-minute tests for C19 and flu ‘hugely beneficial
- Two new tests for C19 that are said to deliver results within 90 minutes are to be introduced across NHS hospitals and care homes in the United Kingdom, to speed up diagnosis ahead of winter and differentiate coronavirus infection from flu, the government says.
- But some experts were surprised by the government’s decision, saying the particular tests were not well-known. No data had been published concerning their evaluation. The government had made mistakes in buying tests that turned out to be sub-standard in the past, they said.
- “Repeatedly through the pandemic the government has raced ahead purchasing tests on the basis of manufacturer’s claims, and have found later when independent studies are done that the tests do not have adequate performance for use in the NHS,” said Professor Jon Deeks from Birmingham University, part of a team who have been evaluating tests of this sort.
- “We would hope that the government would wait for proper evaluations, and consider the scientific evidence for all available tests before signing further contracts. The mistakes made in test purchasing have wasted millions of pounds as well as put lives at risk.”
- One of the new tests is made by DnaNudge, a company that analyses people’s DNA from saliva in order to sell them a wristband and smartphone app that will “nudge” them towards healthy food choices. “We’re all different because our genetic make-up is different, in fact your DNA is unique to you. This genetic code also determines which foods are good or bad for us,” says its website.
- Their C19 test, using nasal swabs, will be rolled out across NHS hospitals from September. The company is supplying 5,000 “Nudgeboxes” that process the tests, up to 15 a day, with the aim to provide 5.8m tests in the coming months, said the Department for Health and Social Care. The boxes have already been trialled in eight London hospitals.
- The other test, called LamPORE, is made by Oxford Nanopore and can analyse saliva as well as nose swab samples. A desktop machine can process 15,000 tests a day and a portable palm machine, which can be taken to outbreaks or institutions where a “pop-up” lab is needed, can do 2,000.
- From next week, 450,000 of the new LamPORE tests will be available across adult care settings, NHS laboratories and lighthouse laboratories, with millions more tests to be rolled out later in the year, said the DHSC.
- “We’re using the most innovative technologies available to tackle coronavirus. Millions of new rapid coronavirus tests will provide on-the-spot results in under 90 minutes, helping us to break chains of transmission quickly,” said health secretary Matt Hancock.
- “The fact these tests can detect flu as well as C19 will be hugely beneficial as we head into winter, so patients can follow the right advice to protect themselves and others.
- “I am hugely grateful for the excellent work done by DnaNudge and Oxford Nanopore to push forward these life-saving innovations in coronavirus testing.”
- Prof Deeks said he and colleagues had not come across either of the new tests. “We cannot emphasize how important it is to see independent evaluations of all tests before they are implemented. Both of these technologies are new, and it is unclear what evaluations have been done. We cannot find any independent studies or even claims about their performance on the company websites. They are not listed on the main international lists of available and approved tests.”
- Deenan Pillay, professor of virology at UCL, also said he worried that the government was purchasing tests that were yet to be fully evaluated, particularly outside of the usual healthcare settings.
- “They may be very good, and if so that’s great (although the data must be made available for scrutiny, and to avoid any suspicion of conflicts of interests),” he said.
- But the critical component of all diagnostic tests, however good, is the pathway from identifying those who need it and obtaining appropriate samples through to getting the results and ensuring action is taken, be it contact tracing or helping those with a positive test to get advice and care.
- “Since this [test] now includes other viruses in addition to covid which may circulate widely in winter then the list of potential actions are amplified,” he said.
3. Mass C19 Testing Will Not Achieve Anything Other Than Take Resources Away
- Canadian associate Chief Medical Officer of Health Dr. Barbara Yaffe warned against mass C19 testing so that resources can be reallocated to test and treat only suspected cases.
- Dr. Yaffe opened with, “A lot of people think that testing is going to really solve the whole problem, and it isn’t. It’s one component of a response. If you test somebody today, you only know if they’re infected today. And in fact, if you’re testing in a population that doesn’t have very much COVID, you’ll get false positives almost half the time. That is, the person actually doesn’t have COVID. They have something else. They may have nothing.”
- Dr. Yaffe continues, “So it will just complicate the picture. On the other hand, if we have evidence of a case, even a suspect case in a school, all the contacts of that case, be it a child or a teacher, would be tested regardless of whether they’re symptomatic or not. That is something we’ve learned with COVID. It’s very important to do that. That is when we might be identifying people who are asymptomatic and infected that need to stay home and wait till they’re cleared by Public Health. Doing testing on all the teachers would be a huge amount of resources taken away from the need for quick access to testing when somebody may be symptomatic.”
- Dr. Yaffe states, “We also need to do screening for symptoms and everybody needs to be educated about the symptoms to look for and not go to work if you’re sick. Not go to school if you’re sick. Those are the things that are important, along with handwashing, distancing, masking all the things we’re talking about. Testing will not actually achieve anything other than take resources away from other places.“
E. Improved & Potential Treatments
1. Eli Lilly is testing a way to prevent C19 that’s not a vaccine
- Nurses and patients in some US assisted living facilities will receive an antibody drug to prevent C19 infection, according to drug company Eli Lilly.
- Early in the coronavirus pandemic, companies searched the blood of C19 survivors for potent antibodies against the novel virus. Eli Lilly’s drug is one of these Y shaped proteins—it’s a natural antibody manufactured at a larger scale.
- To carry out the study, which will involve 2,400 people, Lilly will work with the National Institutes of Health to target nursing homes with C19 outbreaks. In some areas, elderly residents in nursing homes account for the majority of C19 deaths.
How it works:
- Just like natural antibodies, Lilly’s antibody should grab onto the virus and block it. Similar antibody treatments proved effective in treating Ebola disease, but the goal here is to prevent infection by giving the drugs earlier. Prevention with antibodies is known to work. There is an antibody shot given to babies that prevents RSV, a respiratory infection striking newborns.
- Vaccines expose the body to a part of the pathogen, leading to “active immunity”—your body learns to makes its own antibodies against a germ. Adding antibodies artificially generates “passive” immunity which lasts only as long as the antibodies. Researchers say antibodies, delivered usually via an IV, can stay in the bloodstream for weeks or months.
- Antibody treatments could reach the market before a vaccine. It could be a big deal for protecting health care workers and the most vulnerable. A report today from the American Biodefense Institute calls passive immunity “the next generation of pandemic response.”
2. Critically ill C19 patients make quick recovery with treatment RLF-100
- Critically ill C19 patients recovered rapidly from respiratory failure after three days of treatment with RLF-100, a therapy granted fast-track designation in the United States, two drug companies said Sunday.
- Geneva-based Relief Therapeutics Holdings has a patent for RLF-100, or aviptadil, a synthetic form of a natural peptide that protects the lung. US-Israeli NeuroRx Inc. partnered with Relief to develop the drug in the United States.
- In June the FDA granted fast-track designation to RLF-100 for treatment of respiratory distress in C19.
- While a Phase 2/3 clinical trial with 70 patients is ongoing, RLF-100 is being administered on an emergency basis to some patients who are too ill to be admitted to the trial.
- The first report of rapid recovery under emergency use was posted by doctors from Houston Methodist Hospital, the companies said in a joint statement.
- It said a 54-year-old man who developed C19 while being treated for rejection of a double lung transplant came off a ventilator within four days of treatment with RLF-100.
- Similar results were subsequently seen in more than 15 patients treated under emergency use, the companies said.
- The two companies also said independent researchers in a biocontainment laboratory in Brazil reported that aviptadil blocked replication of the SARS coronavirus in human lung cells and immune cells.
3. Next big C19 treatment may be manufactured antibodies
- As the world awaits a C19 vaccine, the next big advance in battling the pandemic could come from a class of biotech therapies widely used against cancer and other disorders – antibodies designed specifically to attack this new virus.
- Development of monoclonal antibodies to target the virus has been endorsed by leading scientists. Anthony Fauci, the top U.S. infectious diseases expert, called them “almost a sure bet” against C19.
- When a virus gets past the body’s initial defenses, a more specific response kicks in, triggering production of cells that target the invader. These include antibodies that recognize and lock onto a virus, preventing the infection from spreading.
- Monoclonal antibodies – grown in bioreactor vats – are copies of these naturally-occurring proteins.
- Scientists are still working out the exact role of neutralizing antibodies in recovery from C19, but drugmakers are confident that the right antibodies or a combination can alter the course of the disease that has claimed more than 675,000 lives globally.
- “Antibodies can block infectivity. That is a fact,” Regeneron Pharmaceuticals executive Christos Kyratsous told Reuters.
- Regeneron is testing a two-antibody cocktail, which it believes limits the ability of the virus’ to escape better than one, with data on its efficacy expected by late summer or early fall. “Protection will wane over time. Dosing is something we don’t know yet,” said Kyratsous.
- The U.S. government in June awarded Regeneron a $450 million supply contract. The company said it can immediately begin production at its U.S. plant if regulators approve the treatment.
- Even with that unusual cooperation among rivals, manufacturing these medicines is complex and capacity is limited. There is also a debate over whether a single antibody will be powerful enough to stop C19.
- AstraZeneca said it plans to start human trials of its dual-antibody combination within weeks.
- Lilly, which began human testing in June of two antibody candidates in separate trials, is focusing on a one-drug approach.
- “If you need a higher dosage or more antibodies, fewer people can be treated,” Lilly Chief Scientific Officer Dan Skovronsky said.
- Unlike vaccines, which activate the body’s own immune system, the impact of infused antibodies eventually dissipates.
- Still, drugmakers say monoclonal antibodies could temporarily prevent infection in at-risk people such as medical workers and the elderly. They could also be used as a therapeutic bridge until vaccines become widely available.
- “In a prophylactic setting we think we may achieve coverage for up to six months,” said Phil Pang, chief medical officer of Vir Biotechnology, which aims to start testing an antibody in non-hospitalized patients next month with partner GSK.
- “The advantage of an antibody is that it is basically instant immunity,” said Mark Brunswick, senior vice president at Sorrento Therapeutics, which aims to begin human trials next month of a single antibody candidate.
- Safety risks for monoclonal antibodies are considered low, but their cost can be quite high. These types of drugs for cancer can cost over $100,000 a year.
- There is also concern that the coronavirus could become resistant to specific antibodies. Researchers are already at work on second-generation compounds with targets other than the crown-like spikes the virus uses to invade cells.
- “We are trying to develop something that is complementary,” Amgen research chief David Reese said. Amgen is working with Adaptive Biotechnologies Corp.
- Researchers in a recent paper published in the journal Nature said they had discovered several new, very potent, antibodies directed to an area where the virus attaches to human cells and to a region of the spike that has not attracted attention.
- “To avoid development of resistance you want to target different sites,” study author and Columbia University professor David Ho told Reuters.
- There are also questions about when in the course of the illness it might be best to employ these new weapons.
- “Giving an antibody later on after infection might not be that helpful, said Florian Krammer, microbiology professor at New York’s Icahn School of Medicine. “Given early, they probably work well.”
4. New published study identifies potential C19 treatment
- Yunjeong Kim and Kyeong-Ok “KC” Chang, virologists in the College of Veterinary Medicine at Kansas State University, have published a study showing a possible therapeutic treatment for C19.
- Pathogenic coronaviruses are a major threat to global public health, as shown by severe acute respiratory syndrome coronavirus, or SARS-CoV; Middle East respiratory syndrome coronavirus, known as MERS-CoV; and the newly emerged coronavirus (SARS-CoV-2).
- The study, “3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV-infected mice,” appears in the Aug. 3 issue of the prestigious medical journal Science Translational Medicine (here). It reveals how small molecule protease inhibitors show potency against human coronaviruses. These coronavirus 3C-like proteases, known as 3CLpro, are strong therapeutic targets because they play vital roles in coronavirus replication.
- “Vaccine developments and treatments are the biggest targets in C19 research, and treatment is really key,” said Chang, professor of diagnostic medicine and pathobiology. “This paper describes protease inhibitors targeting coronavirus 3CLpro, which is a well-known therapeutic target.”
- The study demonstrates that this series of optimized coronavirus 3CLpro inhibitors blocked replication of the human coronaviruses MERS-CoV and the coronavirus in cultured cells and in a mouse model for MERS. These findings suggest that this series of compounds should be investigated further as a potential therapeutic for human coronavirus infection.
- Chang and Kim have been using National Institutes of Health grants to develop antiviral drugs to treat MERS and human norovirus infections. Their work extends to other human viruses such as rhinoviruses and the coronavirus.
F. Concerns & Unknowns
1. Nearly half of coronavirus patients at NYC hospital developed kidney issues
- Nearly half of coronavirus patients admitted to Manhattan’s Mount Sinai Hospital developed acute kidney problems — even though the vast majority had never had any issues with the organ before, according to a new report.
- The find came in a study of nearly 4,000 pandemic patients to pass through the hospital between Feb. 24 and May 30, CNBC reported Monday.
- 46% of patients developed some sort of kidney injury during their C19 battles, the study found.
- For 17%, the affliction was so severe that they required dialysis — and more than a third of patients who beat the virus didn’t regain the same kidney function they had before.
- And most of the patients who developed problems — 82% — had never experienced any prior issues with their kidneys, according to the study.
- Dr. Alan Kliger, co-chair of the American Society of Nephrology’s C19 Response Team, told the network that the finding is hardly limited to Mount Sinai.
- “What we have observed is that approximately 10% to 50% of patients with severe C19 that go into intensive care have kidney failure that requires some form of dialysis,” Kliger told CNBC.
- There’s no one explanation for exactly how the virus decimates the kidneys.
- Some biopsies have found that the virus directly affects the organ, Kliger said.
- Other evidence shows that C19 can trigger a “cytokine storm” — an overreaction by the immune system that hurts one’s kidneys and other vital organs in the process of trying to fight off the contagion.
- In some extreme cases, the coronavirus can trigger sepsis, and with it, multiple organ failure, according to Kliger.
- There is also evidence that life-saving ventilators can have the unintended side effect of restricting blood flow through the kidneys, potentially damaging them even as they see patients through the virus’ respiratory attacks.
- Dr. Steven Coca, associate professor of nephrology at Mount Sinai Health System, told CNBC that once the coronavirus is defeated, the next battle will be against its lingering effects on survivors’ kidneys.
- “Since the start of the coronavirus pandemic, we have seen the highest rate of kidney failure in our lifetimes,” he told the network. “The next epidemic will be chronic kidney disease in the US among those who recovered from the coronavirus.”
2. Survivors of C19 show increased rate of psychiatric disorders
- More than half of people who received hospital treatment for C19 were found to be suffering from a psychiatric disorder a month later, a study has found.
- Out of 402 patients monitored after being treated for the virus, 55% were found to have at least one psychiatric disorder, experts from San Raffaele hospital in Milan found. The results, based on clinical interviews and self-assessment questionnaires, showed post-traumatic stress disorder (PTSD) in 28% of cases, depression in 31% and anxiety in 42%. Additionally, 40% of patients had insomnia and 20% had obsessive-compulsive (OC) symptoms.
- The findings will increase concerns about the psychological effects of the virus. The paper, published on Monday in the journal Brain, Behavior and Immunity, says: “PTSD, major depression, and anxiety are all high-burden non-communicable conditions associated with years of life lived with disability.
- “Considering the alarming impact of C19 infection on mental health, the current insights on inflammation in psychiatry, and the present observation of worse inflammation leading to worse depression, we recommend to assess psychopathology of C19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.”
- The study of 265 men and 137 women found that women – who are less likely to die from Covid than men – suffered more than men psychologically. Patients with positive previous psychiatric diagnoses suffered more than those without a history of psychiatric disorder. The researchers, led by Dr Mario Gennaro Mazza, said these results were consistent with previous epidemiological studies.
- They said psychiatric effects could be caused “by the immune response to the virus itself, or by psychological stressors such as social isolation, psychological impact of a novel severe and potentially fatal illness, concerns about infecting others, and stigma.”
- Outpatients showed increased anxiety and sleep disturbances, while – perhaps surprisingly – the duration of hospitalisation inversely correlated with symptoms of PTSD, depression, anxiety and OC.
- The researchers said: “Considering the worse severity of C19 in hospitalized patients, this observation suggests that less healthcare support could have increased the social isolation and loneliness typical of C19 pandemics.”
- They said their findings mirrored those from previous studies in outbreaks of coronaviruses, including Sars, where the psychiatric morbidities ranged from 10% to 35% in the post-illness stage.
- There have been warnings from UK experts about brain disorders in C19 patients. Problems including brain inflammation, stroke and psychosis have been linked to the virus.
G. The Road Back?
1. Vaccine Confronts Humanity With Next Moral Test
- The coronavirus pandemic has stress-tested the world. Beyond challenging human fortitude, national health services and international rivalries, it has forced a series of moral choices. Many have provoked impassioned disagreement — over whether governments can force businesses and schools to close, over sacrifices for the sake of the elderly and, most bitterly and surprisingly, over whether being asked to wear a simple face mask infringes individual liberty.
- The toughest moral test lies ahead. The biomedical industry and research facilities around the world are progressing toward creating a vaccine that would offer the best chance to end the pandemic and return life to normal. But the moral dilemmas provoked by the development and distribution of a vaccine will drive ever deeper debates.
- The issues strike at profound divisions between schools of ethics. The newly published “Ethics and Pandemics,” an anthology edited by philosophy professor Meredith Schwartz of Ryerson University in Toronto, presents contrasting views of academics, doctors and commentators along with a series of impossibly difficult case studies. The scientific, economic and political choices involve moral issues that have divided ethicists for centuries:
How to Develop It?
- The U.S government says the C19 vaccine will be developed “at warp speed.” But vaccines take years to develop, for good reasons, and none of the benefits can be realized if they are released before they are safe. A failed C19 vaccine could even compromise confidence in other vaccinations, threatening a return of measles, polio and other plagues.
- Testing shortcuts are available but fraught. The first rule of deciding when they’re justified, explains Arthur Caplan, the head of bioethics at the NYU Langone hospital system in New York, is that risks can be balanced against the prospect of better data. Thus, skipping animal testing may pass muster since the data from testing humans is better.
- That leads to the issue that divides teams at Moderna Inc. in Boston and at Oxford University in England who are working on the two most promising attempts to find a vaccine. How much risk of harming humans can they justifiably take? The best way to accelerate the process could fall afoul of the long-established obligations of medical ethics, from the Hippocratic oath to “do no harm.”
- That pledge is as old as ancient Greece, it aligns with Christian teaching, and with the powerful school of rights-based philosophy identified with the 18th-century German philosopher Immanuel Kant, which holds that people should never treat humanity as a means to an end. Whatever the ultimate positive consequences, Kantians argue, there is no right to harm anyone. Virtuous ends do not justify unethical means.
- In “human challenge trials,” which have been used to test cholera and dengue vaccines, volunteers are injected with a vaccine and then deliberately infected with the germ that researchers are hoping to neutralize. The subjects are tightly monitored, and results are available within weeks. Researchers at Oxford are developing strains of the coronavirus in preparation for such a trial alongside a much larger conventional study, as are the National Institutes of Health in the U.S. Such a study will require 150 volunteers at the most.
- Moderna opted against human challenge trials, and instead started a conventional trial with 30,000 test subjects in July. Volunteers are given either the vaccine or a placebo, and then go about their daily lives as the pandemic rages. Moderna hopes to have scientifically reliable results by the end of the year.
- Tal Zaks, Moderna’s chief medical officer, said he expects this approach to reveal how the vaccine behaves with different groups of people and in different regions. By testing in the real world, he said, results can be superior to the outcome of challenge tests, which are held in laboratory conditions.
- But the conventional approach is slower, and leaves much to chance. Oxford’s attempt to hold such a study in London and Oxford earlier this year came just as the epidemic was beginning to decline in the U.K., making it hard to draw firm conclusions. A rival research team at Imperial College, London, has the same problem and is looking to hold a trial in another country.
- Further, doctors are morally obliged to tell volunteers how to avoid getting infected. They cannot tell them to go maskless, or to seek out crowded spaces, even though from a narrowly scientific point of view this would improve their test results. It’s also impossible to monitor so many volunteers closely enough to determine if they are reporting their experiences inaccurately and skewing the results.
- Rutgers University bioethicist Nir Eyal says that coronavirus challenge testing in the U.S could simultaneously “maximize utility and respect rights.” Researchers would use only “informed, willing, low-risk volunteers” from a population that is already in high-risk areas, he said.
- Volunteers are abundant. An advocacy group called 1 Day Sooner has found 32,000 volunteers in 140 countries, all between the ages of 20 and 30, (old enough to consent but much less exposed to serious harm from C19 than their elders) with no relevant underlying medical conditions. Strongly believing in effective altruism, Josh Morrison, who heads 1 Day Sooner, voluntarily donated one of his kidneys to a stranger, as did others helping with the campaign.
- But Kantian objections are serious. Michael Rosenblatt, a Harvard Medical School professor and former chief medical officer of Merck Inc., objects that human challenge studies should only be contemplated when some lifesaving treatment, such as an antiviral medicine, is available for a candidate who gets sick. There is no such cure for C19.
- Then there is the problem of the unknown. Vaccines must pass muster with libertarians, descended from figures such as the enlightenment philosopher John Locke and the founding fathers of the U.S., who build morality around individual freedom. To counter libertarian objections, researchers must obtain “informed consent.”
- Rosenblatt argues that when it comes to C19, “It’s pretty hard to have informed consent when we barely know anything about this yet.” There are fears that the virus can cause lasting damage even in twentysomethings, for example, but little clear evidence. Can volunteers really consent to expose themselves to such poorly understood risks?
- Finally, there is the appalling possibility of a volunteer dying. In 1999, this happened to Jesse Gelsinger, a healthy 18-year-old with a rare metabolic genetic disorder who volunteered for a conventional safety trial (not a challenge trial) of a virus-based gene therapy. His death was both a personal tragedy and a scientific disaster that “set the field of gene therapy back by at least two decades,” Rosenblatt said. “That hiatus deprived a generation of patients with genetic disorders of treatments.”
- Morrison, of 1 Day Sooner, defends the right to volunteer for testing. Estimates at present are that the risk of death from C19 for people in their 20s with no pre-existing conditions is under one in 10,000 — less than the risk of dying in childbirth while soldiers (whether volunteer or conscripted) face a far higher chance of dying on the battlefield.
How to Ration It?
- The pharmaceutical industry cannot produce enough vaccine for the entire global population of almost 8 billion all at once. Therefore, rationing is inevitable. Some people will have to wait. Who gets to make these decisions, and by what criteria?
- Within the U.S., various medical bodies and government agencies claim authority to draw up the guidelines. No one seems empowered to adjudicate.
- “The principle is to protect those most likely to be harmed,” said Caplan of NYU Langone. That leads to one point of clarity: Medical workers go first. They’re obviously at risk, and have a duty to put themselves in harm’s way.
- But after this, following his criterion leads to prioritizing some of the least privileged in society – not because they are underprivileged and deserve help, but because they are most at risk.
- Statistically, prisoners follow doctors and nurses on the list of people most likely to be harmed. As prisons are C19 incubators, Caplan suggests that vaccinating inmates would limit the disease’s spread.
- Within the U.S., Native-American communities are grievously affected, and therefore have a case for priority. The same is true of some other ethnic minorities, largely because they tend to live in crowded communities, and because higher rates of poverty make them more likely to suffer the underlying conditions that make C19 more deadly.
- People are also more at risk if they cannot work from home. Anthony Skelton, a philosophy professor at the University of Western Ontario, makes a case for sending those in work-at-home professions to the back of the line.” To the extent that racial minorities might live and/or work in conditions that make them less able to avoid coming into contact with infected individuals, the case for giving them priority over people who can work from their home office seems strong,” Skelton said.
- All of these proposals spring from prioritizing people according to risk, but might in practice look like the kind of redistributionist social-justice crusading that provokes controversy, particularly in the U.S.
- Rationing could also be affected by where the vaccine was tested. In the case of AIDS, experimental treatments were assessed in Africa, where testing was cheaper, but the treatments then went to developed countries. Severely affected African countries had to pay prohibitive prices as the disease took hold.
- Africa could become a C19 test site if regulators do not permit human challenge tests elsewhere. If large-scale testing does happen there, justice will demand that early supplies of the vaccine are made available to Africans, even at the expense of people in the researchers’ home country.
How to Roll It Out?
- Vaccinations work best when everyone receives them, since germs that can’t infect people tend to wither away.
- But all vaccines come with risks. That creates a “free-rider” problem. The best option from a self-interested point of view is that everybody else has the shot (eliminating your personal risk of catching C19) – but that you don’t (avoiding any personal risk of side-effects). Taxes have the same problem. Taxes are compulsory. Does that mean vaccination should be compulsory, too?
- The public-health case for compulsion is strong. But libertarians have a problem with forcing a potentially harmful vaccine on someone without the “informed consent” that’s hard to procure in societies skeptical of experts and low on social trust.
- How can the vaccine reach a critical mass without compulsion? Caplan suggests leaving compulsion to private entities. An employer might demand vaccination as a condition of reporting for work. A university might impose the same requirement on faculty and students. A vaccine might be dangled as a golden ticket to return to theaters, cinemas, night clubs or sports events. Governments or foundations could even pay people to receive a shot.
- By this thinking, those who assert their right not to be vaccinated would be free to work from home and home-school. They would be voluntarily narrowing their own freedom of movement and assembly.
- Yet societies would pay a price. The virus has divided humans in countless ways already. If many citizens opt to stay unvaccinated, the virus and the messy ethics of compelling vaccination will have helped to create another permanent division.
H. Back to School!?
1. Germany, Denmark Are Models For How To Reopen Schools In The Age Of C19
- With the fall semester officially starting this week in some parts of the US, the question of how public schools will reopen for the fall semester, and how much in-person learning to allow, if any, is weighing on the minds of millions of Americans.
- And while we await to learn more about New York’s plans for reopening its schools, a team of economists at Goldman Sachs took a close look at the existing data surrounding the virus’s ability to spread in schools, and among younger children, along with the economic costs of keeping schools closed, in an attempt to answer a critical question: How exactly should the US go about reopening its schools?
- Looking at the problem from a strictly medical perspective is difficult enough. The research that exists is often contradictory:
- One large study based on comprehensive contact tracing in South Korea found that children under 10 were roughly half as likely as adults to transmit the virus to others, while children between the ages of 10 and 19 transmitted the virus at similar rates to adults.
- Other studies appear to show children spreading the virus at similar rates to adults, including one study focusing on a summer camp in Georgia.
- Another study found that children may carry higher viral loads, suggesting that they could put adults around them at high risk of infection.
- It’s fair to assume at this point that children are at less risk of infection and death, but that’s about all we can say for sure. As always, the bigger problem is what are the societal ramifications in terms of infection numbers?
- The usefulness of these studies is clearly limited. With that in mind, governments should instead look to the handful of examples where schools successfully have reopened without triggering the virus to come roaring back.
- We’ve repeatedly cited the experience of Denmark as a potential guiding light for the US, and the rest of Europe, when it comes to reopening schools.
- Goldman takes this analysis a few steps further, looking at an even broader scope of countries that have reopened schools cautiously and carefully, despite having only limited numbers of the infected.
- Still, Belgium, France and Germany certainly saw substantial outbreaks, even if the virus may not have penetrated as deeply, in as many parts of their countries, as it did in the US.
- American states could probably learn a thing or two from the judicious approach favored by Germany, France and Belgium.
- And if that isn’t enough to drive home the point, Goldman argues that Israel’s approach stands in stark contrast to Europe: Israel reopened classes with as many as 40 students, and few restrictions. Cases quickly flared back up, suggesting that reopening must be carefully monitored.
- Here’s a more detailed breakdown of how various countries approached reopening their schools.
- Sweden, as Goldman points out, never closed its schools. And although it’s not a focus of the report, its example certainly warrants close scrutiny.
- To be sure, the process of reopening schools in the US will require a much more detailed explanation. Approaches will vary widely from state to state, with Georgia, Indiana and a handful of other states pushing ahead with the return to in-person instruction, even as cases from the outbreak’s second wave have only just begun to decline.
- But motivated by the second wave and parents’ lingering fears, a growing number of states are pushing back start dates for in-person learning. Some states have left the decision up to individual counties – and some counties like Miami-Dade have been steadfast in their opposition to pressure from the statehouse and Washington.
- In many cases, local school districts will decide when to reopen.
- Like with many other aspects of the government response to the pandemic, keeping schools closed places the biggest strain on the most vulnerable members of society, especially single parents…
- …but also married couples. Regardless, without schools open, a large chunk of the labor force will require support in the form of child care to make a return to full-time work plausible.
- While keeping schools closed comes with a tremendous economic pricetag, since not only are educators out of work, but parents, too, struggle to secure affordable childcare, putting their jobs at risk. This can seriously suppress productivity and labor-market growth.
- But in the worst-hit states, the risks of thousands of preventable deaths are simply too great to justify pressing ahead.
- Successfully reopening schools will ultimately depend less on infection rates among students, but on infection rates among parents, teachers and coaches.
I. Projections & Our (Possible) Future
1. C19 Vaccine Could Mean Regular Injections, No Guarantee Of Immunity
- While Dr. Anthony Fauci says he’s hopeful that a C19 vaccine will be available ‘by late fall or early winter,’ it may not be as simple as one jab for a lifetime of immunity, according to the LA Times.
- For starters, a C19 vaccine can be released if it’s ‘safe and proves effective’ on as few as 50% of those who receive it, according to recently released federal guidelines. What’s more, the definition of “effective” means that it simply has to ‘minimize the most serious symptoms,’ according to the report.
- “We should anticipate the coronavirus vaccine to be similar to the influenza vaccine,” said Dr. Kathleen Neuzil, director of the Center for Vaccine Development at the University of Maryland. “That vaccine may or may not keep people from being infected with the virus, but it does keep people out of the hospital and the ICU.”
- Because of this, experts say that the first round of C19 vaccines probably won’t eliminate the need for masks, social distancing and other measures.
- So – after all the promises made by government officials, a vaccine may only reduce symptoms, and may turn into a recurring shot that only works on half the population.
- Developing a vaccine capable of inducing “sterilizing immunity” — that is, the ability to prevent the virus from causing an infection — takes time and research, which might not be possible as death tolls continue to rise and the recession grows deeper. Yet with so many companies on the hunt for that vaccine, there is hope one of them might actually achieve it.
- Scientists had studied other coronaviruses — SARS and MERS — and mapped the novel coronavirus’ genome not long after the first C19 deaths were recorded. They identified the spike protein on the virus’ outer shell, which the virus uses to infiltrate the host cell and created a three-dimensional model of the virus to see how antibodies block infection by binding onto the spike protein.
- Even so, scientists don’t yet know what immunity against the virus looks like. That information typically comes from studying the body’s natural response to disease. The number of T-cells and neutralizing antibodies that fight off an infection can become a blueprint for a vaccine. –LA Times
- The problem is that “the novel coronavirus hasn’t been around long enough,” according to Dr. Mark Feinberg, CEO of the International AIDS Vaccine Initiative – who noted that an Ebola vaccine went from Phase 1 to Phase 3 clinical results in just 10 months and was nearly 100% effective within 10 days of a single dose being administered.
- On the bright side, it could reduce the spread of the virus, creating pockets of immunity throughout the country according to Dr. Peter Hoetz, dean of Baylor College of Medicine’s National School of Tropical Medicine.
- “Ideally, you want an antiviral vaccine to do two things,” said Hotez. “First, reduce the likelihood you will get severely ill and go to the hospital, and two, prevent infection and therefore interrupt disease transmission.”
- For the current pandemic, “the bar does not seem that high,” he added.
- Meanwhile, Operation Warp Speed – the Trump administration’s program to accelerate a vaccine, has a goal of delivering 300 million doses by January. The program has identified 14 ‘promising candidates‘ – of which seven have been identified as front-runners. Of those, three have had early clinical trials evaluated independently.
- The vaccine being developed by Moderna and the National Institutes of Health was deemed “promising” in an editorial published in the New England Journal of Medicine, and two studies in the Lancet delivered a similar message for vaccines being developed at Oxford University and by the Chinese company CanSino.
- These vaccines have induced an immune response in people participating in early tests, but inducing an immune response does not always mean success in fighting a disease. For instance, scientists recently developed a vaccine for another respiratory virus that increased antibodies but failed its Phase 3 clinical trial. –LA Times
- Other issues puzzling vaccine researchers include why some people produce high levels of neutralizing antibodies to C19, while others do not.
- “What’s interesting is that all have recovered, and we do not know how they did this,” said Feinberg – former chief public and health science officer at Merck.
- Moreover, scientists don’t know how long immunity lasts, and whether a noted decline in antibodies after just 2-3 months will complicate efforts to find a lasting cure.
- “If we get a vaccine that is 60% efficacious, we can use the information to identify what distinguishes people who are protected from those who are susceptible,” Feinberg added. “Then we will know what the minimum target is for an immune response.”
- No wonder 70% of Americans are planning to wait to get the vaccine – or won’t get one at all, according to a poll from CBS News – which notes that just 27% of those over 65 would get the vaccine right away, while liberals are twice as likely than conservatives to get one immediately.
2. A Vaccine May Not Be The “Magical Cure” Everyone Anticipates
Few appear willing to follow the probabilities of a future in which a vaccine cannot possibly be the “magic cure” everyone wants.
- Can any corona-virus vaccine achieve 99% effectiveness? And for how long? There is some science-based skepticism that a corona-virus vaccine that works for virtually everyone and is effective for a year or longer is even achievable.
- If the reliability/effectiveness is significantly less than 99%, that introduces a Russian-Roulette type risk calculus in those getting the vaccine. What if I’m one of the unlucky folks who get the virus despite getting the vaccine?
- If the duration of efficacy is variable–maybe it works for a year for most people but considerably less for a significant percentage of those who get the vaccine–then that also introduces the same risk assessment: how can I know if the vaccine will protect me for a full year?
- Since Nature often tracks a Pareto Distribution–the 80/20 rule–let’s make some preliminary estimates based on that. Let’s say that the vaccine is 80% effective, and 80% of the populace agrees to get the vaccine. (Let’s set aside the reasons why 20% of the populace might decide not to get the vaccine regardless of its purported effectiveness or the penalties placed on those who refuse.)
- The U.S. population is around 330 million, and let’s estimate that institutionalized residents might not be given a choice about getting the vaccine.
- So perhaps 10 million people won’t have a choice in the matter. That leaves 320 million with a choice. If 20% refuse for various reasons, that’s 64 million who will be unvaccinated and 256 million who choose to get the vaccine.
- If the vaccine is effective in 80% of these 256 million people, then 205 million will receive the benefits of the vaccine and 51 million might come down with the virus (perhaps in milder cases, perhaps not–that will have to be determined by large-scale double-blind studies).
- Again following the Pareto Distribution, let’s estimate that 20% of the 256 million people who get the vaccine will choose to avoid higher-risk settings such as cruises, concerts, etc., even though they’ve been vaccinated, because the uncertainty increases their caution. This would be entirely understandable and prudent in at-risk populations such as those older than 60, those with pre-existing conditions, etc.
- As I explained in Consumer Spending Will Not Rebound–Here’s Why (May 18, 2020), this older, at higher-risk cohort happens to collect the lion’s share of household income and own the lion’s share of household wealth. Their decisions to limit participation in riskier activities have an outsized economic impact because they collect almost half the income and own about 85% of all household wealth.
- Following the 80/20 rule, we end up with 64 million unvaccinated and 51 million vaccinated who choose to avoid higher-risk activities. That’s 115 million people who will not resume their pre-pandemic lifestyles either because they may be barred from activities because they’re not vaccinated or because their at-risk profile and the inherent uncertainties of the vaccine cause them to avoid higher-risk activities.
- Those assuming that requiring vaccination to board a airliner will boost vaccination to nearly 100% could be underestimating the strength of the motivations of those who decide not to get the vaccine. It would also be unwarranted to assume that everyone who chooses not to get the vaccine is a rabid anti-vaxxer.
- Given the latent uncertainties and the self-interest of those pushing for a rapid approval of a vaccine, it would be entirely prudent to choose to let the first wave of residents get the vaccine and then await the results of large-scale studies of efficacy, duration, etc.
- Given the rapacious greed of Big Pharma corporations and their track record of playing fast and loose with claims of safety and efficacy, we can also anticipate multiple vaccines battling for market share, a struggle that will create incentives to inflate claims of efficacy and marginalize side-effects.
- As for bans on air travel, concerts, etc. for the unvaccinated, many people will simply drop out of the mainstream economy. The wealthy will book seats on private charter aircraft and hire performers in open-air venues, etc., the unwealthy will seek unconventional options and give up flying, going to sports events, etc.–activities they may no longer be able to afford anyway.
- What kind of economy will we have if a third of the populace–100+ million people–are no longer participating at pre-pandemic levels for one reason or another? An accurate description might be The Greater Depression.
- Few appear willing to follow the probabilities of a future in which a vaccine cannot possibly be the “magic cure” everyone wants.
- Some percentage of the populace will not be participating in the economy at pre-pandemic levels for one or more of these reasons:
- They choose not to be vaccinated.
- They choose to be vaccinated but remain cautious in their activities and spending.
- They no longer have the income or wealth to resume their 2019 level of borrowing/spending.
- Lastly, imagine the impact if a few people die of the virus after getting the vaccine. Human risk assessment does not necessarily track probabilities like a computer. Assuring everyone that only 1% of the recipients of the vaccine become ill or die within a year will not be as reassuring as proponents hope.
3. Why A Return To Lockdowns Isn’t A Smart Strategy For Suppressing C19’s “Second Wave”
- A team of macro analysts from JP Morgan’s sell-side research desk published a lengthy paper aggregating all of their C19-related findings. And while perusing the note, one particular finding caught our eye. In one section of the note, the team addressed a critical question for epidemiologists (and investors): Will the amount of time required to reach “peak” infection rates vary between successive “waves” of the virus? And if so, how might this inform the global policy response?
- Succeeding in compressing the “half life” of the wave should be the central focus of policy makers, the analysts argued. And while globally, the policy response in country after country has favored lockdowns, Melbourne is showing right now that, especially when case numbers are small relative to the overall population, lockdowns might not make sense as the most effective way to contain the virus.
- As the infection curve starts to resurge in many countries, signaling the next wave, we examine whether the time to arrive at the peak is similar in both the first and second waves. Conceptually, we develop a hypothesis on shorter potential lifespan for the infection curve as the curve moves into the next waves.
- In our view, the concept of decay in ‘half-life’, i.e. the time required for a quantity to reduce to half, could be applicable to picturing the next waves.
- We think (1) better secondary infection rate control, (2) large mobility tracing and more voluntary testing; and, (3) shorter recovery periods could drive a shorter curve peak.
- It is not necessarily so that if more people are infected, a larger part of society would have antibodies and that this would flatten the curve. We note that, in most countries – both developed and developing – the size of infection is only 0.2-0.5% of the total population.
- Even if we were to assume about 5x higher unreported infection cases, this is still relatively small. Also, “ring vaccination” is not a strategy yet, as so far we do not have a vaccine widely available for the public.
- Over the coming 6-12 months, JPM analysts concluded, it’s likely that a number of factors resulting from lessons learned during the first wave will commingle to help shorten the trough-to-peak dynamic in the ensuing waves.
- For the record, this is how the team calculates “secondary infection rate” =, or “R sub zero”, their preferred means of measuring the rate of viral spread.
- Here are JPM’s reasons for believing that R-sub-zero will be more restrained during upcoming waves, including the second and third waves that appear to be rising in Asia and Europe at present:
- Sample size (So): Declining. This is due to the large scale of tests conducted and the government push for identification of C19 at an early stage.
- Also, the technology tracking infections seems to suggest that the size of susceptible population is smaller than in the last couple of months.
- Transmission rate: Rising. Mandatory guidance on wearing a mask in public places seems to be working as the key factor to control the rate of transmission. That said, we believe this is not enough to offset rising human mobility. After reopening, the transmission rate is likely to rise, as social distancing measures are relaxed, human mobility increases, and there is the risk of airborne transmission.
- Average duration of recovery: Shortening. As the government ramps up the medical resources and gains more experience in treating the infections, the average duration of recovery is shortening.
- All of this suggests that since we likely won’t be able to entirely suppress the virus without a vaccine, the world needs to rethink its approach to keeping cases at bay, and try to find a happy medium that will allow the economy to function as well as possible.
- Another important difference between the first wave and the emerging second wave that researchers have observed is the fact that the second wave appears to arrive in smaller, more isolated clusters centered around a particular point of vulnerability (like the house parties in New Jersey and Connecticut).
- Sample size (So): Declining. This is due to the large scale of tests conducted and the government push for identification of C19 at an early stage.
- How does the JPM analysts’ theory hold up against our current research? Admittedly, there’s not a ton of data on there about the onset of second waves. What exists suggests that the theory could very prove reliable. Though, presumably if not enough is done, it also might prove a failure.
- Bottom line: Governments need to recognize that small levels of C19 infection will likely need to be tolerated, and attended to with more sustainable measures, like mandatory social distancing, remote or distanced learning and other techniques. Perhaps Sweden’s approach will emerge as an example. Perhaps not.
- To minimize damage to the economy will maximizing survival rates and minimizing mortality, governments should build a consensus on the ‘no riskfree’ next step in society (i.e., that the public should accept that a certain number of confirmed cases may exist in society until a vaccine becomes widely available) and that we will all need to do our part to contain the spread once the economy begins to reopen. But moving forward with more lockdowns probably isn’t a reliable solution.
- In many countries, like India, it’s simply not an option.
J. Johns Hopkins COVID-19 Update
August 3, 2020
1. Cases & Trends
- The WHO C19 Situation Report for August 2 reports 17.7 million cases (262,929 new) and 662,095 deaths (5,999 new). The WHO reported the 2 highest daily incidence to date on July 31 and August 1—292,527 and 289,321 new cases, respectively. If the current trend continues, the global daily incidence could potentially exceed 300,000 new cases for the first time later this week. The average global daily incidence is nearly 260,000 new cases per day, putting the pandemic on pace for approximately 1.8 million cases per week. Asia is now reporting the most new cases, but North and South America remain close at #2 and #3, respectively. Africa and Europe have reported similar daily incidence since late June. The global C19 mortality is holding relatively steady at approximately 5,700 new deaths per day, which corresponds to more than 170,000 deaths per month.
- Following a long period of declining daily incidence from approximately early April through mid-June, Europe is exhibiting what could be the early signs of a resurgence of C19 transmission. A number of European countries—including Spain, France, and Germany, which were severely affected early in the pandemic—are reporting increasing C19 incidence. Overall, Europe’s daily incidence is at a similar level as where it was in late May, but not nearly as high as it was at the first peak in early April. The increased incidence comes several weeks after the EU began to ease social distancing measures and travel restrictions and the beginning of Europe’s summer holiday and tourism season. No European countries are in the top 10 globally in terms of daily incidence, but several are reporting more than 1,000 new cases per day.
South & Central America
- Brazil reported approximately 6,000 fewer cases last week than the previous week, but it was the second consecutive week that it reported more than 300,000 new weekly cases. Brazil remains #3 globally in terms of daily incidence but fell slightly further behind India. Broadly, the Central and South American region remains a major C19 hotspot. Colombia surpassed 300,000 cumulative cases and 10,000 deaths. Colombia reported 11,470 new cases, a record high daily incidence for the second consecutive day. Colombia climbed to #4 globally in terms of daily incidence. Mexico’s average daily incidence exceeded 7,000 new cases per day for the first time on August 2 before falling slightly below that mark today. Mexico remains #6 globally in terms of daily incidence. Including Brazil, Colombia, and Mexico, the Central and South American region represents 5 of the top 10 countries globally in terms of daily incidence, along with Peru (#7) and Argentina (#9), and multiple other countries in the region are reporting more than 1,000 new cases per day. Additionally, the region includes 4 of the top 10 countries in terms of per capita daily incidence—Panama (#1), Brazil (#3), Colombia (#5), and the US (#7)—and numerous other countries are reporting more than 100 new daily cases per million population.
India & Bangladesh
- India reported its 5 highest daily case counts over the past 5 days, including a record high of 57,118 new cases on August 1. India remains #2 globally in terms of daily incidence and appears to be on a trajectory to potentially surpass the US. Bangladesh reported extremely low incidence on August 1-2—886 and 1,356 new cases, respectively. Notably, this dramatic decrease corresponded to elevated test positivity (32% on August 2), which could indicate that it is more likely a result of decreased testing than decreased incidence.
- The Philippines climbed to #10 in terms of daily incidence, with an average of more than 3,200 new cases per day.
- South Africa surpassed 500,000 cumulative C19 cases over the weekend and reported 8,195 new cases yesterday. South Africa remains among the top countries globally in terms of both per capita (#9) and total daily incidence (#5). Additionally, South Africa is #5 globally in terms of cumulative incidence.
- The per capita daily incidence in the Eastern Mediterranean region appears to be waning to some degree, and countries from several other regions are displacing the Eastern Mediterranean in the top 10. Bahrain (#4) is the only country remaining in the global top 10, and Kuwait is the only other country in the region reporting more than 100 new daily cases per million population. Nearby Israel (#8), in the WHO’s European region, remains among the top countries globally as well. Iraq fell out of the top 10 in terms of total daily incidence, but numerous countries in the region are reporting more than 1,000 new cases per day.
Maldives & Montenegro
- The Maldives climbed to #2 globally in terms of per capita daily incidence, with more than 225 new cases per day per million population. Montenegro fell to #10 in terms of per capita daily incidence.
- The US CDC reported 4.60 million total cases (58,947 new) and 154,002 deaths (1,132 new). The US has reported more than 1,000 new deaths for 10 of the past 12 days, and it is currently averaging more than 1,100 new deaths per day, the highest average since May 25. California surpassed 500,000 cases; Florida is reporting nearly 475,000; New York and Texas are reporting more than 400,000; and 9 additional states are reporting more than 100,000.
- The Johns Hopkins CSSE dashboard reported 4.68 million US cases and 154,992 deaths as of 12:45pm on August 3.
2. US Schools
- The US school year is rapidly approaching in many parts of the country and has even started in some jurisdictions. With some evidence now available from experiences in summer camps, childcare settings, and the early days of in-person classes, the focus is shifting from what could happen if schools reopen toward what has happened—and the news is not encouraging. A case study published in the US CDC’s Morbidity and Mortality Weekly Report describes an outbreak at an overnight summer camp in Georgia that resulted in at least 260 confirmed infections out of 597 total campers and staff, between when staff reported to the camp and 14 days after the camp was closed due to the outbreak. This corresponds to an overall attack rate of approximately 44%. Notably, test results were only available for 344 individuals, so this may be an underestimate. Among the individuals with positive tests, 136 had accompanying data on the presence or absence of symptoms, and 100 of those individuals were symptomatic (73.5%). Campers and staff were required to provide proof of a negative test conducted within 12 days of arriving at camp, and the camp implemented a number of recommended preventive measures.
- Notably, however, masks were only required for staff, not campers, and the camp did not open windows to improve indoor ventilation. This case study does not address any subsequent transmission by campers or staff to others at home or in the community after departing the camp. Regardless, this outbreak does illustrate that SARS-CoV-2 can “spread efficiently in a youth-centric overnight setting, resulting in high attack rates among persons in all age groups” and that “children of all ages…might play an important role in transmission.”
- Two junior and senior high schools in Madison County and Hancock County, Indiana, were reportedly forced to close this week, shortly after resuming in-person classes, due to positive SARS-CoV-2 tests among students and staff. In Georgia, approximately 260 employees in the state’s largest school district tested positive for SARS-CoV-2 or are under quarantine due to possible exposure as the school district began in-person meetings in preparation for resuming classes in the coming weeks. The New York Times reported that only 6 of the 25 largest school districts in the country plan on reopening for in-person classes when the school year starts. The New York Times also published analysis on the number of positive cases that could be expected to show up at a school, based on the level of community transmission and school size.
- It is unclear if or how the reports of cases at other schools or projections of cases in schools will influence the debate around school reopening. A number of health experts and officials—including CDC Director, Dr. Robert Redfield; White House Coronavirus Task Force Response Coordinator, Dr. Deborah Birx; and former US FDA Commissioner, Dr. Scott Gottlieb—have expressed concern about the viability of resuming in-person classes, particularly in areas with high community transmission. Notably, Dr. Redfield commented last week that, while in-person classes are important for children, schools in areas with test positivity above 5% may need to utilize remote learning instead, at least initially, to mitigate transmission risk among children.
- Spain was among the most severely affected countries early in the C19 pandemic, reaching its first peak of nearly 8,000 new cases per day in early April. Following highly restrictive “lockdown” measures, implemented in conjunction with other EU countries, Spain brought its epidemic under control. By mid-June, Spain’s daily incidence had fallen to fewer than 350 new cases per day. As the EU began to ease social distancing and travel restrictions, C19 began to rebound, prompting fears of a “second wave” across the continent. After several weeks of steadily increasing daily incidence, Spain now leads Europe* with 2,300 new cases per day.
- Much like the US, Spain’s C19 resurgence includes an increasing proportion of cases among younger individuals. Notably, the average of C19 cases in Spain “has fallen from 63 [years old] in the spring to 45 now,” which has fortunately placed less stress on the health system. Some of the increased incidence can be attributed to improved testing capacity, but the trend remains concerning. Spain’s test positivity is down from more than 20% in April to less than 5% now, but it has been increasing slowly since early June, an indication that the increased testing is not fully accounting for the increased incidence. Some parts of Spain—including Catalonia, where Barcelona is located—have reinstituted some social distancing measures, such as closing nightclubs and mandating mask use in public, in order to slow transmission. Additionally, the recent increase in C19 incidence drove the UK government to implement a mandatory 14-day quarantine for travelers arriving from Spain.
- Over the weekend, Colombia passed the milestones of 300,000 cases and 10,000 deaths, and its epidemic continues to accelerate. Colombia remains one of the major hotspots in Central and South America, and health systems and other sectors are struggling to combat the epidemic. Reportedly, hospitals in Bogotá, Colombia’s capital city, are on the verge of being overwhelmed by C19 patients, and the government has provided refrigeration units for cemeteries that are unable to keep up with cremation demand for C19 victims.
- Colombia’s Ministry of Health provided support to local hospitals to expand intensive care unit (ICU) capacity and stave off collapse, and the Mayor of Bogotá implemented quarantine and curfew for severely affected parts of the city, currently scheduled from July 31 through August 14. Armed groups in some parts of the country, including paramilitary groups associated with drug cartels, have reportedly begun using gunfire and other violent means to enforce curfews. It appears that the groups are leveraging the C19 epidemic to consolidate control over local populations rather than support recommended health actions. One report by Human Rights Watch identified these types of “lockdowns” in 11 of 32 states across Colombia.
5. Vaccine Candidates
- Several candidate SARS-CoV-2 vaccines have initiated Phase 3 clinical trials, which are much larger and will provide a wealth of detailed safety and efficacy data over the course of the next several months. While these candidate vaccines have demonstrated promise in previous trials, numerous barriers remain to implementing a successful global mass vaccination campaign. Dr. Tom Frieden, former US CDC Director, authored an editorial in The Wall Street Journal to discuss some of these challenges.
- Vaccines in Phase 3 trials have already demonstrated acceptable safety profiles and exhibited promising efficacy in smaller Phase 1 and 2 trials, but Phase 3 trials will involve tens of thousands of people, as opposed to dozens or hundreds, which will allow researchers to better characterize the vaccines’ effects on the immune system and identify a broader range of potential adverse events. One outstanding question, in particular, regarding the vaccine’s efficacy is the degree and duration of the conferred immunity. In an ideal scenario, the vaccine would confer long-term immunity, on the order of years, 100% of the time.
- However, it is possible that like the seasonal influenza vaccine, a SARS-CoV-2 vaccine could be only partially effective at preventing infection or C19 disease, which could potentially limit its effect in the public. Additionally, it is possible that the vaccine could only remain effective for a short period of time, potentially on the order of months, which would necessitate regular vaccination or booster shots to ensure individuals maintain immunity to SARS-CoV-2. The Phase 3 trials will allow researchers to analyze longer-term trends in immune response, including both the degree and duration of the associated immune response. Phase 3 trials could also identify rarer adverse events that were not evident in the smaller Phase 1/2 trials. Even if the vaccines continue to demonstrate acceptable safety profiles in the larger Phase 3 trials, continued surveillance will be needed as vaccination programs scale up to millions and then billions of people to identify any additional adverse events that may arise in larger populations. Based on historical trends, it is inevitable that some candidate vaccines, potentially including those already entering Phase 3 trials, will fail to reach the public due to safety or efficacy issues during clinical trials. Regardless of which vaccine, or vaccines, successfully obtains regulatory approval, scaling up production, distributing the vaccine worldwide, and dispensing it to every individual will be a monumental task.
6. Tropical Storm Isaias
- Tropical Storm Isaias continues to threaten the East Coast of the US, with a hurricane warning in effect for North Carolina and South Carolina, but the storm is expected to impact communities beyond wind, rain, and flooding. The storm was originally forecasted to impact Florida directly, which drove the state to preemptively close all state-run C19 testing centers from Friday through this Tuesday—although some reopened early when the storm veered north. The Coastal Health District in Georgia also closed C19 testing sites in advance of the storm.
- North Carolina declared a state of emergency and ordered evacuations for some parts of the state. Additionally, the state advised residents to include specific items in emergency kits to protect against C19, such as masks, hand sanitizer, and cleaning products. North Carolina Governor Roy Cooper recommended that evacuees stay with friends or family or in a hotel, if possible, in order to reduce the population at emergency shelters, which could be higher risk for SARS-CoV-2 transmission. Shelters will implement C19 preventive measures, including symptom screening, reduced capacity to promote physical distancing, mandatory mask use, and serving meals in sealed containers. Georgia and South Carolina have not declared states of emergency, but both states issued similar recommendations regarding the use of shelters as a last resort. Emergency shelters in both Georgia and South Carolina will also implement similar enhanced safety precautions for C19. Emergency management officials in Georgia noted that physical distancing and reduced shelter capacity, in particular, pose challenges for evacuation plans, as officials must find more buses and shelters in unaffected areas and coordinate additional logistics for those resources.
7. World Health Organization
- On July 30, the WHO published updated guidance for international travel. Many countries have implemented some form of travel restrictions, ranging from prohibitions on travelers from certain countries or areas to screening or self-quarantine upon arrival. The new WHO guidance emphasizes that decisions regarding when and how to lift existing travel restrictions should be made based on careful risk assessments, and they should prioritize essential travel activities, such as emergency response, humanitarian assistance, and repatriation of citizens or residents. Similarly, cargo and shipping companies should prioritize the transport of essential supplies, including as medicine and food. Prospective passengers who are feeling ill and individuals at an elevated risk of severe C19 disease or death should postpone travel, particularly to areas with sustained community transmission. The guidance document also includes recommended actions for travelers, such as testing prior to travel and enhanced hygiene, physical distancing, and mask use while traveling.
- On July 31, WHO Director-General Dr. Tedros Adhanom Ghebreyesus convened the fourth meeting of the IHR (2005) Emergency Committee regarding the C19 pandemic. Following the meeting, the Director-General declared that C19 continued to constitute a Public Health Emergency of International Concern. Additionally, the Emergency Committee issued guidance to the WHO Secretariat regarding priorities for coordinating the international response—including on mobilizing resources, combating misinformation, and issuing travel guidance—and to national governments, specifically with respect to supporting multilateral response efforts, enhancing public health response capacity, and information sharing.
8. Another Cruise Ship Outbreak
- Following a number of high-profile C19 outbreaks onboard cruise ships around the world early in the pandemic, many cruise lines suspended operations over concerns about C19 risk to passengers and crew. Hurtigruten cruise line, operating out of Norway, is one of the first companies to resume operations, but it was forced to suspend all of its cruises after an outbreak of at least 40 passengers and crew. Initially, 4 crew members onboard the MS Roald Amundsen tested positive for SARS-CoV-2, and an additional 32 crew and 4 passengers tested positive during subsequent testing.
- After identifying the outbreak, passengers and crew on the ship were placed in quarantine, and the cruise line suspended operations. Notably, the ship visited multiple ports in Norway in the days leading up to the first positive tests, including shore excursions and passengers embarking and disembarking at various ports along the way. These visits could have resulted in exposures in “dozens of towns and villages along Norway’s western coast” by passengers or crew who were asymptomatic or presymptomatic at the time. The cruise line emphasizes that it operates in compliance with all guidance from the Norwegian Institute of Public Health, but the outbreak highlights the risk of rapid transmission in congregate settings like cruise ships, even with enhanced social distancing and sanitization standards in place.