Weekend Edition
September 20, 2020
Without reliable information, we rely on fear or luck.
Index
A. Numbers & Trends
B. New Scientific Findings & Research
3. People who wear eyeglasses may be at lower risk for catching C19 (!)
4. Biomarker predicts who will have severe C19
5. Study suggests substantial proportion of pet cats and dogs are infected with coronavirus by their owners (Link Only)
6. Scientists uncover the structural mechanism of coronavirus receptor binding (Link Only)
7. Study shows high prevalence of fatigue following coronavirus infection independent of C19 disease severity (Link Only)
8. Study shows coronavirus jumped between people and mink, providing strong evidence of zoonotic transmission (Link Only)
9. Studying the Genetic Evolution of Viruses Like Coronavirus in Single Cells Could Reveal New Ways to Defeat Them (Link Only)
10. First Proof That a Safer UV Light Effectively Kills Coronavirus (Link Only)
11. Faster-Acting, Longer-Lasting Coronavirus Disinfectant Under Development (Link Only)
C. Improved & Potential Treatments
1. Potential new drug to mitigate coronavirus infection consequences
2. New method identifies antibody-like proteins with diagnostic and therapeutic potential for coronavirus (Link Only)
D. Immunity
1. Do many people have pre-existing immunity? (!)
E. Concerns & Unknowns
1. The Most Likely Way You’ll Get Infected With C19 (*)
2. Why fit, healthy women are the most at risk of long Covid (!)
3. An ‘uncoordinated’ immune response may explain why C19 strikes some hard, particularly the elderly
4. ‘A Very Serious Situation’: WHO Says Coronavirus Cases Are Rising In Europe Again
5. Study shows one quarter of hospitalized young patients aged 18-39 years with C19 developed pneumonia (Link Only)
6. Stroke patients with C19 have increased inflammation, stroke severity and death (Link Only)
7. Health-care workers make up 1 in 7 C19 cases recorded globally, WHO says (Link Only)
F. Back To School!?
1. As schools spend big on temperature check tech, experts warn: It won’t work
G. The Road Back?
1. How to Live With Covid, Not for It
H. Lockdowns
1. By the numbers, it’s hard to see how lockdowns saved many lives
I. Projections & Our (Possible) Future
1. A Military-Funded Biosensor Could Be the Future of Pandemic Detection (!)
J. Practical Tips & Other Useful Information
1. The Odds of Catching Covid on a Flight Are Slim (*)
K. Johns Hopkins COVID-19 Update
A. Numbers & Trends
Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the prior day.
Sources: https://www.worldometers.info/coronavirus/ and https://covidtracking.com/
1. Cases & Tests (9/19)
Worldwide Cases:
- Total Cases = 30,976,621
- New Cases = 291,222
- New Cases (7 day average) = 284,070 (+374) (+0.1%)
Observations:
- 7 day average was a record high
- 7 day average continues to increase, but growth rate as slowed over the last few days
- 1,000,000+ new cases every 4 days
US Cases & Testing:
- Total Cases = 6,967,403
- New Cases = 42,533
- New Cases (7 day average) = 41,113 (+464) (+1.1%)
- Percentage of New Global Cases (7 day average) = 14.5%
- Total Number of Tests = 97,310,312
- Percentage of positive tests (7 day average) = 6.0%
Observations:
- Although 7 day average is 40.7% lower than the 2nd peak on 7/25, it has been steadily increasing since 9/12
- 7 day average has increased 16.8% since 9/12, which is a concern
2. Deaths
Worldwide Deaths:
- Total Deaths = 960,872
- New Deaths = 5,142
- New Deaths (7 day average) = 5,228 (+16) (+0.3%)
Observations:
- 7 day average has been trending lower since 2nd peak on 8/3
- 7 day average has declined 11.7% since 2nd peak
US Deaths:
- Total Deaths = 203,824
- New Deaths = 657
- New Deaths (7 day average) = 796 (-8) (-1.0%)
- Percentage of Global New Deaths (7 day average) = 15.2%
Observations:
- 7 day average is 31.3% lower than 2nd peak on 8/4
- 7 day average has been trending lower since 2nd peak, with a period increases between 9/9 and 9/15
3. Top 5 States in Cases, Deaths, Hospitalizations, and Positivity (9/19)
Observations — Positivity and Hospitalizations
- A total of 31 states have average 7-day positivity rates in excess of the recommended 5.00%
- Despite the high positivity rates for the top 5 states, the growth in hospitalizations has yet to materialize, and the states have more than enough capacity at the current positivity rates.
Hospitalizations | |||
State | 9/5/20 | 9/19/20 | Available Beds |
North Dakota | 67 | 78 | 1,545 |
Wisconsin | 275 | 342 | 5,365 |
South Dakota | 86 | 153 | 1,806 |
Wyoming | 15 | 16 | 1,069 |
Idaho | 151 | 146 | 1,818 |
Source: IHME, Worldometer and The Covid Tracking Project
B. New Scientific Findings & Research
1. Interim data from early US C19 hotspot show mortality and seriousness of disease were not associated with race/ethnicity
- A study of interim data from two hospitals in an early US C19 hotspot, to be presented at the ESCMID Conference on Coronavirus Disease (ECCVID, held online 23-25 September), shows that race and ethnicity were not significantly associated with higher in-hospital C19 mortality, and that rates of moderate, severe, and critical forms of C19 were similar between racial and ethnic groups.
- The study, by Dr Daniel Chastain (University Of Georgia College Of Pharmacy, Albany, GA, USA) and colleagues included data from adult patients hospitalized between March 10 and and May 22 with C19, defined by laboratory-detected coronavirus 2 (SARS-CoV-2), in Southwest Georgia.
- The authors compared severity of illness categories on presentation to the hospital between patients from different racial and ethnic groups based on criteria from the US National Institutes of Health (NIH) C19 treatment guidelines. They also studied outcomes including comorbidities, laboratory values, vital signs, and in-hospital mortality.
- A total of 164 randomly selected non-consecutive patients were included with a median age of 61.5 years. These consisted of 119 African American patients, 36 Caucasian patients, and 9 Latinx patients. Thus the majority were African American (73%) and 51% were female. Rates of moderate, severe, and critical C19 did not significantly differ between African American (9%, 56%, and 35%), Caucasian (0%, 69%, and 31%), and Latinx patients (0%, 56%, and 44%). In-hospital mortality was not statistically significantly different between groups but was highest among Caucasians (31%) followed by Latinx (22%) and African Americans (16%).
- Caucasian patients had significantly higher Charlson comorbidity index scores (meaning more underlying conditions) (4.5) compared to African American (4) and Latinx (2) patients, while median BMI was significantly higher in African Americans (33.7 kg/m2) than in Caucasians (26.9) or Latinx patients (25.9).
- Duration of time from symptom onset to admission was similar between groups, whereas median temperature on admission was significantly higher in African Americans (38.3oC) than in Caucasians (37.9) or Latinx patients (37.8)
- The authors conclude: “Despite the majority of our cohort being African American, the rates of moderate, severe, and critical forms of C19 were similar between racial and ethnic groups in a major transmission hotspot during the early spread of the pandemic in the Southeastern US. Race and ethnicity were not significantly associated with higher in-hospital mortality…our results were similar to findings from other recent studies from the states of Massachusetts and Louisiana. However, since this is an interim analysis, there is a possibility that these results were due to chance. We are in the process of conducting additional follow-up studies with a larger sample size.”
2. Coronavirus: constantly surprising virus found to be heat tolerant, self-healing and very resilient in lab tests
- A research team in Hungary pinched the coronavirus with a fine needle to measure how much force it could take before popping like a balloon. It did not.
- The native virion of the coronavirus – a complete virus particle – was only about 80 nanometres wide, and the needle tip was much smaller than that. The tip drove from the top of the virus to the bottom. The virion was squashed, then immediately rebounded as the needle left.
- The researchers repeated the drill 100 times and the same viral particle remained almost intact.
- It is “surprisingly resilient,” said the team led by Dr Miklos Kellermayer of Semmelweis University in Budapest in a non-peer-reviewed paper posted on biorxiv.org on Thursday.
- The new coronavirus has constantly surprised scientists with its unique structure. For instance, a team from Tsinghua University in Beijing released the most detailed structural reconstruction of the virus in the journal Cell this week with the discovery that the virus could pile a large amount of nucleic acid ribbon that carries genetic data into a very tight envelope without the two becoming entangled.
- However, the virus used in this and other previous studies was frozen to obtain a sharp, stable shot for the camera.
- Kellermayer’s team captured how the virus behaved when it was alive. They put the viral particles on a tray coated with a biological binding material.
- The material could fix the virus in position. Under a laser-emitting atomic force microscope, the scientists played around with the virus with a needle to see how it responded to various stimuli.
- A virus usually becomes vulnerable after leaving the host. But according to some studies, the coronavirus could stay on some everyday surfaces such as cupboards for several days.
- How it managed to survive environmental disturbances remained unclear.
- The Hungarian team found the viral envelope barely gave any resistance as the needle tip landed on the surface. As the tip went further, the resisting force peaked and then quickly diminished to almost non-existent.
- Their experimental data suggested the coronavirus could be the most physically elastic virus ever known to humans so far, and repeated deformation did not seem to affect the overall structure and the content inside the virus, either.
- “Its mechanical and self-healing properties may ensure adaptation to a wide range of environmental circumstances,” said Kellermayer and colleagues.
- Chinese scientists estimated that the coronavirus had on its surface 26 spike proteins that could bind with a host cell. Researchers at Cambridge University in Britain gave a similar estimate of 24. A study by researchers in the Max Planck Institute in Germany came up with a count of 40.
- Kellermayer said there were 61 spikes on their specimen. This suggested the variability of the viral structure could be greater than thought, they said.
- They poked the spike proteins with the needle and found they were swinging rapidly at high frequency. The atomic camera could take more than 300 shots in a second but still only got a motion-blurred image of the spikes.
- Such high speed movements could help the virus more easily find and hook onto a host cell, according to the researchers.
- A study by French scientists in April found that the virus could replicate in animal cells after being exposed to a temperature of 60 degrees Celsius for an hour. The massive outbreaks in some countries over the northern hemisphere summer also suggested that high temperature did not slow the spread of the pandemic as previously hoped.
- Kellermayer and his colleagues heated the viral particle to 90 degrees for 10 minutes and found that “remarkably, their global appearance was only slightly altered”.
- Some spikes had come off under the scorching heat, but the overall structure remained intact.
- “The coronavirus virion displays an unexpected global thermal stability, which is likely related to their aerosol and surface stabilities,” they said.
Source: Coronavirus is heat tolerant, self-healing and very resilient in lab tests
3. People who wear eyeglasses may be at lower risk for catching C19
- People who wear eyeglasses may be at lower risk for catching C19 than those who don’t wear glasses, early research from China suggests.
- The study researchers analyzed information from 276 patients at a hospital in China’s Hubei province and found that only about 6% said they wore glasses for more than 8 hours a day, all of whom had myopia, or nearsightedness. That’s much lower than the estimated rate of myopia in Hubei from previous research, which was 31.5%.
- The new study, published Wednesday (Sept. 16) in the journal JAMA Ophthalmology, “is provocative and raises the possibility that use of eye protection by the general public might offer some degree of protection from C19,” Dr. Lisa Maragakis, an associate professor of medicine and epidemiology at Johns Hopkins University School of Medicine, who was not involved in the study, wrote in an editorial accompanying the study.
- However, Maragakis cautions that it’s much too early to recommend that everyone don eyeglasses, goggles or face shields in public, in addition to already wearing face masks, to protect against C19. The new study has a number of limitations — for starters, the study was relatively small and included patients at a single hospital. Importantly, the study found only an association and cannot prove a “cause-effect” relationship between wearing glasses and being protected from C19, Maragakis said.
- Maragakis called for more studies to confirm the findings and to determine “whether there is any incremental benefit to wearing eyeglasses or other forms of eye protection in public settings, in addition to wearing a mask and physical distancing, to reduce the risk of acquiring [C19].”
Eye protection
- Although it’s recommended that health care workers wear face shields or goggles, along with face masks, to lower the risk of catching C19, public health guidelines generally don’t promote the use of eye protection for the public; they instead stress the importance of masks, physical distancing and hand washing. (The CDC does not recommend face shields as a substitute for face masks.)
- The study authors, from Suizhou Zengdu Hospital in Suizhou, China, decided to look into the link between eyeglasses and C19 prevention after they noticed that few patients with C19 at their hospital wore glasses.
- They enrolled the 276 patients in their study between Jan. 27 and March 13, 2020. All participants were asked if they wore eyeglasses, how long they wore glasses during the day and why they needed glasses.
- Overall, 30 participants, or about 11%, said they wore glasses, but only 16 participants, or 5.8%, wore glasses for more than 8 hours a day and that was for myopia. (The other 14 participants wore reading glasses.)
- To compare this with the general population, the researcher drew on a study conducted in 1985 among students in Hubei province, which showed that about one-third had myopia, nearly all of whom wore glasses.
- However, Maragakis noted that this comparison group is a limitation of the study because the research took place “decades earlier” and wasn’t specific to Suizhou.
- But in general, myopia is a common condition, estimated to affect 27% of the world’s population in 2010, with the highest prevalence in East Asia, according to the World Health Organization.
- None of the participants in the study wore contact lenses, so whether wearing contact lenses affects the risk of C19 still needs to be studied, the authors said.
Behind the link
- The researchers did not examine why glasses may reduce the risk of C19, but they hypothesize that wearing glasses discourages people from touching their eyes, which would reduce the chances that people transfer virus from their hands to their eyes. It’s known that eye cells have receptors that allow SARS-CoV-2, the virus that causes C19, to enter the body; and the virus has been detected in the eyes of C19 patients.
- Maragakis added that eyeglasses may also “serve as a partial barrier that reduces the inoculum [amount] of virus in a manner similar to what has been observed for cloth masks.”
- “These findings suggest that the eye may be an important infection route for C19, and more attention should be paid to preventive measures such as frequent hand washing and avoiding touching the eyes,” the study authors concluded.
- Still, in addition to further studies to confirm the findings, researchers also need to consider possible unintended consequences of a general recommendation to wear eye protection in public. People who aren’t accustomed to wearing glasses or goggles might actually touch their face more often when removing, replacing or adjusting the eyewear, Maragakis said.
Source: Could wearing glasses lower the risk of COVID-19?
4. Biomarker predicts who will have severe C19
- Airway cell analyses showing an activated immune axis could pinpoint the C19 patients who will most benefit from targeted therapies.
- KAIST researchers have identified key markers that could help pinpoint patients who are bound to get a severe reaction to C19 infection. This would help doctors provide the right treatments at the right time, potentially saving lives. The findings were published in the journal Frontiers in Immunology on August 28.
- People’s immune systems react differently to infection with the coronavirus, ranging from mild to severe, life-threatening responses.
- To understand the differences in responses, Professor Heung Kyu Lee and PhD candidate Jang Hyun Park from the Graduate School of Medical Science and Engineering at KAIST analysed ribonucleic acid (RNA) sequencing data extracted from individual airway cells of healthy controls and of mildly and severely ill patients with C19. The data was available in a public database previously published by a group of Chinese researchers.
- “Our analyses identified an association between immune cells called neutrophils and special cell receptors that bind to the steroid hormone glucocorticoid,” Professor Lee explained. “This finding could be used as a biomarker for predicting disease severity in patients and thus selecting a targeted therapy that can help treat them at an appropriate time,” he added.
- Severe illness in C19 is associated with an exaggerated immune response that leads to excessive airway-damaging inflammation. This condition, known as acute respiratory distress syndrome (ARDS), accounts for 70% of deaths in fatal C19 infections.
- Scientists already know that this excessive inflammation involves heightened neutrophil recruitment to the airways, but the detailed mechanisms of this reaction are still unclear.
- Lee and Park’s analyses found that a group of immune cells called myeloid cells produced excess amounts of neutrophil-recruiting chemicals in severely ill patients, including a cytokine called tumour necrosis factor (TNF) and a chemokine called CXCL8.
- Further RNA analyses of neutrophils in severely ill patients showed they were less able to recruit very important T cells needed for attacking the virus. At the same time, the neutrophils produced too many extracellular molecules that normally trap pathogens, but damage airway cells when produced in excess.
- The researchers additionally found that the airway cells in severely ill patients were not expressing enough glucocorticoid receptors. This was correlated with increased CXCL8 expression and neutrophil recruitment.
- Glucocorticoids, like the well-known drug dexamethasone, are anti-inflammatory agents that could play a role in treating C19. However, using them in early or mild forms of the infection could suppress the necessary immune reactions to combat the virus. But if airway damage has already happened in more severe cases, glucocorticoid treatment would be ineffective.
- Knowing who to give this treatment to and when is really important. C19 patients showing reduced glucocorticoid receptor expression, increased CXCL8 expression, and excess neutrophil recruitment to the airways could benefit from treatment with glucocorticoids to prevent airway damage. Further research is needed, however, to confirm the relationship between glucocorticoids and neutrophil inflammation at the protein level.
- “Our study could serve as a springboard towards more accurate and reliable C19 treatments,” Professor Lee said.
Source: Biomarker predicts who will have severe COVID-19
C. Improved & Potential Treatments
1. Potential new drug to mitigate coronavirus infection consequences
- Scientists from the Department of Cell Biology of the University of Malaga (UMA) and the Andalusian Centre for Nanomedicine and Biotechnology (BIONAND) have made progress in finding new rapid implementation therapies to combat the C19 pandemic, identifying a new drug that could prevent or mitigate the consequences derived from the coronavirus infection.
- In the coming year, a team led by the researchers of the UMA Iván Durán and Fabiana Csukasi will study how 4-Phenylbutiric acid (4-PBA) treatment modulates the inflammatory response produced in severe cases of C19. The project has been financed by the C19 Fund of the Government of Andalusia, with an initial endowment of EUR 90,000 and the possibility of a three-year renewal. First results have already been published in the scientific journal Cytokine and Growth Factors Review.
- The inflammatory process identified in severe cases of coronavirus causes an uncontrolled and excessive release of cytokines -molecules in charge of organizing the body’s defenses- which could even trigger vascular hyperpermeability and multiorgan failure. Controlling such cytokine “storm”, through those controlling them, that is, the infected cells, is precisely what these researchers of the UMA propose.
- “When cells are stressed by infection, they call the cytokines, and the more stressed they are, the more persistent they become, provoking this uncontrolled inflammation. Hence, one possible treatment for C19 is to reduce cellular stress”, explains Durán.
- According to the researcher, repurposing the 4-PBA anti-stress drug, approved for clinical use against other diseases and, hence, easy to apply clinically, could modulate such cellular stress, which is also present in pathologies like diabetes, aging or carcinogenesis, which, in turn, are classified as risk factors for C19.
Identifying risk groups
- “Our preliminary results conducted on animal models have demonstrated that 4-PBA fully curbs mortality caused by respiratory failure derived from cellular stress“, says the professor of the UMA, who further explains that these first studies have also identified the endoplasmic reticulum resident protein “BiP” (Binding Immunoglobulin Protein) -a stress blood marker- as indicator of cellular stress situations, likely to be explored and measured in affected patients.
- This way, as Durán points out, BiP levels, apart from determining the efficacy of 4-PBA treatment, could serve as early indicators of C19 risk groups, establishing a correlation between high levels and the inflammatory severity after the viral infection.
- “There are people already suffering from diseases that cause cellular stress, and when they become infected with coronavirus, they are more likely to fall ill or die. Therefore, if we know that the patient suffers from cellular stress, we can kill two birds with one stone: we can detect susceptibility before infection occurs and know how to treat it in due time”, remarks the scientist of the UMA.
- In order to confirm the effectiveness and security of 4-PBA treatment through in vitro and in vivo studies of cytokine storm and coronvirus infection, the scientists Csukasi and Durán work at the Biomedical Research Institute of Malaga (IBIMA) in collaboration with Dr. José María Reguera and Dr. Javier Sánchez from the Regional University Hospital of Malaga and Virgen de la Victoria University Hospital, respectively, and Deborah Krakow, researcher of the University of California, Los Angeles, as well as the researchers Manuel Mari-Beffa, Gustavo Rico, José Miguel Tejeiro, Rick Visser and David Bagllieto, members of the Bioengineering and Tissue Regeneration Laboratory (LABRET), directed by Professor José Becerra, who are also members of the Cellular Therapy Network, CIBER-BBN and CIBER-NED.
Source: Potential new drug to mitigate SARS-CoV-2 infection consequences
D. Immunity
1. Do many people have pre-existing immunity?
- It seemed a truth universally acknowledged that the human population had no pre-existing immunity to the coronavirus, but is that actually the case? Peter Doshi explores the emerging research on immunological responses
- Even in local areas that have experienced some of the greatest rises in excess deaths during the C19 pandemic, serological surveys since the peak indicate that at most only around a fifth of people have antibodies to the coronavirus: 23% in New York, 18% in London, 11% in Madrid. Among the general population the numbers are substantially lower, with many national surveys reporting in single digits.
- With public health responses around the world predicated on the assumption that the virus entered the human population with no pre-existing immunity before the pandemic, serosurvey data are leading many to conclude that the virus has, as Mike Ryan, WHO’s head of emergencies, put it, “a long way to burn.”
- Yet a stream of studies that have documented coronavirus reactive T cells in people without exposure to the virus are raising questions about just how new the pandemic virus really is, with many implications.
Not so novel coronavirus?
- At least six studies have reported T cell reactivity against coronavirus in 20% to 50% of people with no known exposure to the virus.
- In a study of donor blood specimens obtained in the US between 2015 and 2018, 50% displayed various forms of T cell reactivity to coronavirus. A similar study that used specimens from the Netherlands reported T cell reactivity in two of 10 people who had not been exposed to the virus.
- In Germany reactive T cells were detected in a third of coronavirus seronegative healthy donors (23 of 68). In Singapore a team analysed specimens taken from people with no contact or personal history of SARS or C19; 12 of 26 specimens taken before July 2019 showed reactivity coronavirus, as did seven of 11 from people who were seronegative against the virus. Reactivity was also discovered in the UK and Sweden.
- Though these studies are small and do not yet provide precise estimates of pre-existing immunological responses to coronavirus, they are hard to dismiss, with several being published in Cell and Nature. Alessandro Sette, an immunologist from La Jolla Institute for Immunology in California and an author of several of the studies, told The BMJ, “At this point there are a number of studies that are seeing this reactivity in different continents, different labs. As a scientist you know that is a hallmark of something that has a very strong footing.”
- In late 2009, months after the World Health Organization declared the H1N1 “swine flu” virus to be a global pandemic, Alessandro Sette was part of a team working to explain why the so called “novel” virus did not seem to be causing more severe infections than seasonal flu.
- Their answer was pre-existing immunological responses in the adult population: B cells and, in particular, T cells, which “are known to blunt disease severity.” Other studies came to the same conclusion: people with pre-existing reactive T cells had less severe H1N1 disease. In addition, a study carried out during the 2009 outbreak by the US Centers for Disease Control and Prevention reported that 33% of people over 60 years old had cross reactive antibodies to the 2009 H1N1 virus, leading the CDC to conclude that “some degree of pre-existing immunity” to the new H1N1 strains existed, especially among adults over age 60.
- The data forced a change in views at WHO and CDC, from an assumption before 2009 that most people “will have no immunity to the pandemic virus” to one that acknowledged that “the vulnerability of a population to a pandemic virus is related in part to the level of pre-existing immunity to the virus.” But by 2020 it seems that lesson had been forgotten.
- Researchers are also confident that they have made solid inroads into ascertaining the origins of the immune responses. “Our hypothesis, of course, was that it’s so called ‘common cold’ coronaviruses, because they’re closely related,” said Daniela Weiskopf, senior author of a paper in Science that confirmed this hypothesis. “We have really shown that this is a true immune memory and it is derived in part from common cold viruses.” Separately, researchers in Singapore came to similar conclusions about the role of common cold coronaviruses but noted that some of the T cell reactivity may also come from other unknown coronaviruses, even of animal origin
- Taken together, this growing body of research documenting pre-existing immunological responses to SARS-CoV-2 may force pandemic planners to revisit some of their foundational assumptions about how to measure population susceptibility and monitor the extent of epidemic spread.
Population immunity: underestimated?
- Seroprevalence surveys measuring antibodies have been the preferred method for gauging the proportion of people in a given population who have been infected by the coronavirus (and have some degree of immunity to it), with estimates of herd immunity thresholds providing a sense of where we are in this pandemic. Whether we overcome it through naturally derived immunity or vaccination, the sense is that it won’t be over until we reach a level of herd immunity.
- The fact that only a minority of people, even in the hardest hit areas, display antibodies against the coronavirus has led most planners to assume the pandemic is far from over. In New York City, where just over a fifth of people surveyed had antibodies, the health department concluded that “as this remains below herd immunity thresholds, monitoring, testing, and contact tracing remain essential public health strategies.” “Whatever that number is, we’re nowhere near close to it,” said WHO’s Ryan in late July, referring to the herd immunity threshold.
Calculating the herd immunity threshold
- In theory, outbreaks of contagious disease follow a certain trajectory. In a population that lacks immunity new infections grow rapidly. At some point an inflection in this growth should occur, and the incidence will begin to fall.
- The 1970s gave rise to a theory that defined this inflection point as the herd immunity threshold (HIT) and offered a straightforward formula for estimating its size: HIT=1−1/R0 (where R0 is the disease’s basic reproduction number, or the average number of secondary cases generated by an infectious individual among susceptible people). This simple calculation has guided—and continues to guide—many vaccination campaigns, often used to define target levels of vaccination.
- The formula rests on two assumptions: that, in a given population, immunity is distributed evenly and members mix at random. While vaccines may be deliverable in a near random fashion, from the earliest days questions were raised about the random mixing assumption. Apart from certain small closed populations such as “orphanages, boarding schools, or companies of military recruits,” Fox and colleagues wrote in 1971,21 truly random mixing is the exception, not the rule. “We could hardly assume even a small town to be a single homogeneously mixing unit. Each individual is normally in close contact with only a small number of individuals, perhaps of the order of 10-50.”
- Nearly 50 years later, Gabriela Gomes, an infectious disease modeller at the University of Strathclyde, is reviving concerns that the theory’s basic assumptions do not hold. Not only do people not mix randomly, infections (and subsequent immunity) do not happen randomly either, her team says. “More susceptible and more connected individuals have a higher propensity to be infected and thus are likely to become immune earlier. Due to this selective immunization by natural infection, heterogeneous populations require less infections to cross their herd immunity threshold,” they wrote. While most experts have taken the R0 for coronavirus (generally estimated to be between 2 and 3) and concluded that at least 50% of people need to be immune before herd immunity is reached, Gomes and colleagues calculate the threshold at 10% to 20%.
- Ulrich Keil, professor emeritus of epidemiology from the University of Münster in Germany, says the notion of randomly distributed immunity is a “very naive assumption” that ignores the large disparities in health in populations and “also ignores completely that social conditions might be more important than the virus itself.” He added, “Tuberculosis here is the best example. We all know that the immune system is very much dependent on the living conditions of a person, and this depends very much on education and social conditions.”
- Another group led by Sunetra Gupta at the University of Oxford has arrived at similar conclusions of lower herd immunity thresholds by considering the issue of pre-existing immunity in the population. When a population has people with pre-existing immunity, as the T cell studies may be indicating is the case, the herd immunity threshold based on an R0 of 2.5 can be reduced from 60% of a population getting infected right down to 10%, depending on the quantity and distribution of pre-existing immunity among people, Gupta’s group calculated.
- But memory T cells are known for their ability to affect the clinical severity and susceptibility to future infection, and the T cell studies documenting pre-existing reactivity to the coronavirus in 20-50% of people suggest that antibodies are not the full story.
- “Maybe we were a little naive to take measurements such as serology testing to look at how many people were infected with the virus,” the Karolinska Institute immunologist Marcus Buggert told The BMJ. “Maybe there is more immunity out there.”
- The research offers a powerful reminder that very little in immunology is cut and dried. Physiological responses may have fewer sharp distinctions than in the popular imagination: exposure does not necessarily lead to infection, infection does not necessarily lead to disease, and disease does not necessarily produce detectable antibodies. And within the body, the roles of various immune system components are complex and interconnected. B cells produce antibodies, but B cells are regulated by T cells, and while T cells and antibodies both respond to viruses in the body, T cells do so on infected cells, whereas antibodies help prevent cells from being infected.
An unexpected twist of the curve
- Buggert’s home country has been at the forefront of the herd immunity debate, with Sweden’s light touch strategy against the virus resulting in much scrutiny and scepticism. The epidemic in Sweden does seem to be declining, Buggert said in August. “We have much fewer cases right now. We have around 50 people hospitalized with C19 in a city of two million people.” At the peak of the epidemic there were thousands of cases. Something must have happened, said Buggert, particularly considering that social distancing was “always poorly followed, and it’s only become worse.”
- Understanding this “something” is a core question for Sunetra Gupta, an Oxford University epidemiologist who developed a way to calculate herd immunity thresholds that incorporates a variable for pre-existing innate resistance and cross protection. Her group argues that herd immunity thresholds “may be greatly reduced if a fraction of the population is unable to transmit the virus.”
- “The conventional wisdom is that lockdown occurred as the epidemic curve was rising,” Gupta explained. “So once you remove lockdown that curve should continue to rise.” But that is not happening in places like New York, London, and Stockholm. The question is why.
- “If it were the case that in London the disease hadn’t disseminated too widely, and only 15% have experienced the virus [as serology tests indicate] . . . under those circumstances, if you lift lockdown, you should see an immediate and commensurate increase in cases, as we have observed in many other settings,” Gupta told The BMJ, “But that hasn’t happened. That is just a fact. The question is why.”
- Possible answers are many, she says. One is that social distancing is in place, and people are keeping the spread down. Another possibility is that a lot of people are immune because of T cell responses or something else. “Whatever it is,” Gupta added, “if there is a significant fraction of the population that is not permissive to the infection, then that all makes sense, given how infectious the coronavirus is.”
- Buggert’s study in Sweden seems to support this position. Investigating close family members of patients with confirmed C19, he found T cell responses in those who were seronegative or asymptomatic. While around 60% of family members produced antibodies, 90% had T cell responses. (Other studies have reported similar results.) “So many people got infected and didn’t create antibodies,” concludes Buggert.
Deeper discussion
- T cell studies have received scant media attention, in contrast to research on antibodies, which seem to dominate the news (probably, says Buggert, because antibodies are easier, faster, and cheaper to study than T cells). Two recent studies reported that naturally acquired antibodies to the coronavirus begin to wane after just 2-3 months, fueling speculation in the lay press about repeat infections.
- But T cell studies allow for a substantially different, more optimistic, interpretation. In the Singapore study, for example, SARS-CoV-1 reactive T cells were found in SARS patients 17 years after infection. “Our findings also raise the possibility that long lasting T cells generated after infection with related viruses may be able to protect against, or modify the pathology caused by, infection with the coronavirus,” the investigators wrote.
- T cell studies may also help shed light on other mysteries of C19, such as why children have been surprisingly spared the brunt of the pandemic, why it affects people differently, and the high rate of asymptomatic infections in children and young adults.
- The immunologists I spoke to agreed that T cells could be a key factor that explains why places like New York, London, and Stockholm seem to have experienced a wave of infections and no subsequent resurgence. This would be because protective levels of immunity, not measurable through serology alone but instead the result of a combination of pre-existing and newly formed immune responses, could now exist in the population, preventing an epidemic rise in new infections.
- But they were all quick to note that this is speculation. Formally, the clinical implications of the pre-existing T cell reactivity remain an open question. “People say you don’t have proof, and they’re right,” says Buggert, adding that the historical blood donor specimens in his study were all anonymised, precluding longitudinal follow-up.
- There is the notion that perhaps T cell responses are detrimental and predispose to more severe disease. “I don’t see that as a likely possibility,” Sette said, while emphasizing that we still need to acknowledge the possibility. “It’s also possible that this absolutely makes no difference. The cross reactivity is too small or weak to affect the virus. The other outcome is that this does make a difference, that it makes you respond better.”
- Weiskopf added, “Right now, I think everything is a possibility; we just don’t know. The reason we’re optimistic is we have seen with other viruses where [the T cell response] actually helps you.” One example is swine flu, where research has shown that people with pre-existing reactive T cells had clinically milder disease.
- Weiskopf and Sette maintain that compelling evidence could come through a properly designed prospective study that follows a cohort of people who were enrolled before exposure to the coronavirus, comparing the clinical course of those with and without pre-existing T cell responses.
- Understanding the protective value of pre-existing coronavirus T cell reactivity “is identical to the situation on vaccines,” said Antonio Bertoletti, professor of infectious disease at Duke-NUS Medical School in Singapore. “Through vaccination we aim to stimulate antibodies and T cell production, and we hope that such induction of immunity will protect … but we need a phase III clinical study to really demonstrate the effect.”
- German investigators came to the same conclusion, arguing that their T cell findings represented a “decisive rationale to initiate worldwide prospective studies” mapping pre-existing reactivity to clinical outcomes. Other groups have called for the same thing.
- “At the start of the pandemic, a key mantra was that we needed the game changer of antibody data to understand who had been infected and how many were protected,” two immunologists from Imperial College London wrote in a mid-July commentary in Science Immunology. “As we have learned more about this challenging infection, it is time to admit that we really need the T cell data too.”
- Theoretically, the placebo arm of a C19 vaccine trial could provide a straightforward way to carry out such a study, by comparing the clinical outcomes of people with versus those without pre-existing T cell reactivity to the coronavirus. A review by The BMJ of all primary and secondary outcome measures being studied in the two large ongoing, placebo controlled phase III trials, however, suggests that no such analysis is being done.
- Could pre-existing immunity be more protective than future vaccines? Without studying the question, we won’t know.
Source: Covid-19: Do many people have pre-existing immunity?
E. Concerns & Unknowns
1. The Most Likely Way You’ll Get Infected With C19
- At the beginning of the pandemic in March, Jeffrey VanWingen, MD, a Michigan family physician, scared the bejeezus out of people and infuriated food scientists. During his 13-minute video, which went viral on YouTube and has been viewed over 26 million times, VanWingen tells people that when they come back from the grocery store, they should leave groceries outside for three days, spray disinfectant onto each product, and soak produce in soapy water. His rationale was that those items might carry the novel coronavirus and could potentially infect people after they come into contact with them.
- Six months later, we’ve learned a lot about how the coronavirus spreads, and it turns out most of VanWingen’s tips are largely unnecessary and some are flat-out dangerous (you should never bleach your food, but hopefully you already knew that). Instead of obsessing over objects and surfaces, scientists now say the biggest infection risk comes from inhaling what someone else is exhaling, whether it’s a tiny aerosol or a larger droplet. And while a virus traveling through the air sounds terrifying, the good news is there is a safe, cheap, and effective way to stop the spread: wearing a mask. Here are the three primary pathways of transmission, and what experts know about them six months in.
Surfaces don’t seem to matter as much as originally thought
- The surface or fomite theory — that you’ll get infected by coming into contact with objects that carry the virus, called fomites, like door handles, shopping carts, or packages — was the original leading contender because that’s how scientists and epidemiologists think most respiratory diseases are spread. For example, when a person sick with a cold coughs or sneezes, tiny snot and saliva particles that carry the virus go shooting out of their nose and mouth and land on nearby surfaces. If someone else touches that surface and then touches their mouth, nose, or eyes they could become infected with the virus. This is why we’re supposed to wash our hands before eating or preparing food, and after using public transportation, or touching door handles, especially during cold and flu season.
- “I’m not saying that you can’t get it, that it’s impossible to get it from surfaces, but a very specific set of events have to occur for that to happen.”
- Supporting this idea, an early study published in the New England Journal of Medicine found that coronavirus survived on various surfaces for several days, including 24 hours on cardboard and 72 hours on plastic. Public health organizations recommended hand hygiene as the first line of defense against the virus, and there were runs on Lysol wipes and hand sanitizer at supermarkets and drugstores, the supply chains for which still have not recovered.
- The problem, says Emanuel Goldman, PhD, a professor of microbiology and biochemistry at Rutgers University, is that the experiments those recommendations were based on “were the wrong experiments to do” because they were not representative of how people come into contact with the novel coronavirus in the real world.
- “They started out with a humongous, totally unrealistic amount of virus at the beginning of the experiment, and then, sure enough, they found virus at the end. But they started out with so much more than you would ever encounter in real life,” he says. “You would have to have 100 people coughing and sneezing on one small area of surface to get the amount of virus that was used in the papers that reported the survival of the virus on surfaces.”
- It turns out that despite the catastrophic harm it’s caused, the novel coronavirus is actually quite fragile, and it doesn’t like being out in the open where it can dry up. According to the NEJM paper, the virus’s half-life is a relatively short six hours, meaning that every six hours 50% of the virus shrivels up and becomes inactive or noninfectious. That means if you start with 100 virus particles, after six hours that number halves to 50 particles; six hours later there are 25 virus particles left, and fewer than 10 virus particles remain after 24 hours. However, if there are huge quantities of virus to start, many more will be left behind after each six-hour window, and it will take longer for all of the virus to disintegrate.
- Instead of buying another can of Lysol, maybe invest in an air purifier, more comfortable two-ply cloth masks, or even an outdoor fire pit or space heater.
- “If you start out with a realistic amount, and a realistic amount would be between 10 and 100 virus particles, because that’s what a droplet of a cough or sneeze is likely to have, then your virus is gone in a day,” Goldman says. “Now, I’m not saying that you can’t get it, that it’s impossible to get it from surfaces, but a very specific set of events have to occur for that to happen.”
- Regardless, it’s critical that people keep washing their hands — although that’s something we should all be doing for normal hygiene anyway — but, Goldman says, you don’t have to do anything excessive, like disinfecting your groceries.
Close range droplets are the new leading theory
- In May, the CDC updated its guidelines to state that fomites were not a major source of transmission. Instead, the agency said, the primary route of infection was probably virus-laden droplets — those snot and saliva particles that are at the root of the fomite theory. But instead of worrying about them after they land on surfaces, the bigger concern now is coming into contact with the droplets while they’re still in the air.
- When you expel air — whether it’s by sneezing, coughing, talking, singing, shouting, or even breathing — tiny bits of saliva, ranging in size from an imperceptible mist to visible spittle, are pushed out. Heavier particles fall to the ground relatively quickly and are categorized as droplets, while the tinier particles stay afloat in the air for longer. When talking and breathing, the typical droplet trajectory is about three to six feet, hence the six-foot distancing recommendation. If the droplets are expelled with more force, like with a sneeze or a cough, they can travel further before hitting the earth.
- Being in close contact with someone raises the risk that you’ll be exposed to the small droplets they’re expelling, and many scientists now think that’s how most people become infected with the virus. One reason is that a virus inside a freshly exhaled droplet is more likely to be alive and infectious than a virus that’s been sitting on a doorknob for several hours. The other reason is that, in close range, breathing in the air that someone else just breathed out is going to expose you to a higher quantity of virus particles — called the inoculum — than after the droplets disperse and fall to the ground.
- “It’s not that [surface spread] can’t happen, it’s just that the likelihood is less than if someone was actually right in front of you breathing live virus in their droplets onto you,” says Nahid Bhadelia, MD, an infectious diseases physician and associate professor at the Boston University School of Medicine. “That is a much bigger inoculum, [and] it’s much more likely that there’s a lot more live virus in it, so that’s why it’s a higher risk.”
- As a result, social distancing has become one of the recommended ways to prevent transmission, the idea being that if you stay more than six feet away from someone, you won’t be hit by the majority of their exhaled droplets. Supporting this theory, most people catch the virus from someone they live with and presumably are in frequent close contact with. In one study from China, for example, an infected person had a 17.2% chance of spreading the virus to a family member who lived with them, but just a 2.6% chance of giving it to someone outside the home.
- “I think people have this preconceived notion that if it’s airborne it’s like the measles or like smallpox where it only takes one viral particle to infect you, and this is almost certainly not the case with this coronavirus. Most coronaviruses are probably in the hundreds.”
- However, there have been several documented instances of infections that don’t fit with droplet or surface spread because they happened even when people maintained their distance. Perhaps the most famous example is the choir rehearsal outside of Seattle, Washington, a superspreader event where 52 out of 61 people were infected during a two-and-half-hour practice. What’s notable about this case is that the singers maintained distance from each other and used plenty of hand sanitizer, per safety guidance at the time. Also, the infected person was presymptomatic, so they weren’t coughing or sneezing and projecting droplets further. Despite all this, one person was still able to infect 52 others.
- A study conducted in hamsters in a lab (that’s right, it turns out hamsters are the best animals in which to study coronavirus spread) found similar results in a more controlled environment. The researchers showed that the animals could infect each other not only through direct contact when they were housed in the same cage, but also when they were separated in different cages in the same room. Based on these studies and other mounting evidence, many scientists began to believe that the virus is transmitted through droplets and aerosols, those tiny mistlike particles that can travel farther through air currents and remain afloat for longer.
Aerosol transmission has gradually gained acceptance
- Despite these observations, some public health experts were initially reluctant to say that the virus is airborne, partly because they didn’t want to alarm the public. There are also debates between epidemiologists, virologists, and aerosol engineers about what the word airborne really means — whether the size of the particles or their behavior (how quickly they fall to the ground, whether they can be carried on a gust of air) matters more, and what questions must be answered before a disease can be defined as such.
- Part of the resistance to calling C19 airborne is also rooted in history. For centuries, doctors and scientists didn’t know how diseases spread. One theory was that infections traveled in invisible clouds called miasmas or “bad air.” It wasn’t until the 1860s that Louis Pasteur’s germ theory of disease began to take hold, cemented in the 1890s with the discovery of viruses. As a result, scientists waged a campaign during the early 20th century to discredit the idea of miasmas and airborne spread with the goal of getting the public to take germs — and personal hygiene — seriously.
- “That became the paradigm of epidemiology and infectious diseases from 1910 until now,” says Jose Luis Jimenez, PhD, a professor of chemistry at the University of Colorado, Boulder who specializes in aerosols. “For medicine, during all this time, a disease going through the air is extremely difficult. It’s an outlandish proposition.”
- As a result of this legacy, public health experts initially believed that the coronavirus couldn’t be spread through the air because the presumption was that virtually no diseases were. There have been a few exceptions made over the years, but those were for viruses that are so contagious they couldn’t conceivably be spread any other way — namely, measles and chickenpox.
- “For diseases like measles and chickenpox, because they are extremely transmissible, the evidence became too obvious,” Jimenez says. “They’re so transmissible through the air that it just became undeniable, and they were accepted as transmitted through aerosols.”
- As surprising as it may sound, by comparison, the novel coronavirus is not very contagious. Each person who gets infected with the coronavirus will, on average, spread it to two or three other people. A person with measles will infect 15 others. Jimenez says the WHO initially cited the coronavirus’s relatively low infectious rate as a reason why it couldn’t be spread through the air. “[They] are confusing an artifact of history with a law of nature,” Jimenez says. “They are thinking it is a law of nature that if a disease goes through the air, it has to be extremely contagious.”
- It wasn’t until a public outcry from over 200 scientists that the WHO finally conceded in July that aerosol transmission was possible.
- So if the novel coronavirus is airborne, why isn’t it as contagious as measles? One reason could be that measles is a hardier virus (remember that the coronavirus is relatively fragile) and can survive longer in those tiny aerosols. Another potential difference is the infectious dose — the amount of virus required to start an infection. Scientists still don’t know exactly how much of the novel coronavirus is needed to make someone sick, but it’s likely higher than conventional airborne viruses.
- “What’s the infectious dose via the respiratory route is really probably the last piece of this that isn’t completely answered yet,” says Joshua Santarpia, PhD, an associate professor in the department of pathology and microbiology at the University of Nebraska. “I think people have this preconceived notion that if it’s airborne it’s like the measles or like smallpox where it only takes one viral particle to infect you, and this is almost certainly not the case with this coronavirus. Most coronaviruses are probably in the hundreds.”
- Another question that needed to be answered before many public health experts could accept that the coronavirus was airborne was whether it could even survive in those smaller aerosol particles. Some viruses can’t because they dry up too quickly without a larger liquid droplet to support them. However, many scientists feel this issue has been put to rest with two recent papers (which have yet to be peer-reviewed) that provide what some have called the “smoking gun” for aerosol transmission: live, replicating virus collected from the air of C19 patient hospital rooms.
- “Confidently, what you can say is that things that we consider aerosols, not droplets, have both [viral] RNA and [live] virus in them that is capable of replication in cell culture,” says Santarpia, who led one of the studies. “I think that between the two of [our studies], you can say that aerosols are infectious… meaning that probably we’re looking at something that’s airborne.”
How to protect yourself from all transmission routes
- By now, most scientists and public health experts agree that the coronavirus can be spread by both droplets and aerosols, particularly in close range, although no one knows which is the dominant route of transmission. “I think it’s a false dichotomy to think of this as airborne versus droplet. Most things exist on a range,” Bhadelia says.
- What matters more is whether people know how to properly protect themselves from the virus. Fortunately, the prevention steps for both transmission routes are largely the same: keep your distance and wear a mask. Evidence of the importance of masks, in particular, has been mounting, not only because they trap outgoing particles from escaping, which protects others, but also because they block larger incoming particles from getting into a person’s airways, protecting the mask wearer themselves. And even if some viral particles do get through, the viral dose will still be much smaller, so the person will be less likely to get seriously ill.
- A clear example of the benefits of masks is a recent outbreak in South Korea, in which one woman at a Starbucks infected 27 other customers — whom officials assume were not wearing masks because they were eating and drinking — but none of the employees, all of whom were masked the entire time.
- Aerosol transmission does increase the importance of one additional protective step, which is proper ventilation and air filtration. Airflow, either introducing new air into a room or filtering the existing air, can disperse and dilute any infectious aerosol particles, reducing a person’s potential exposure. Being outdoors is the ultimate ventilation, and for months public health officials have recommended that people socialize outside rather than in. However, with winter and colder temperatures coming, indoor air filtration and adherence to masks will become even more important.
- “The important thing on the public side is air handling, reducing the number of people in enclosed indoor spaces, and wearing a mask,” says Bhadelia. “[Aerosol transmission] explains why indoor settings are so much more important and contribute so much more to new infections than outdoor settings do.”
- Armed with this knowledge, think about how you can make fall and winter safer, both physically and mentally. Instead of buying another can of Lysol, maybe invest in an air purifier, more comfortable two-ply cloth masks, or even an outdoor fire pit or space heater. Be prepared to meet friends outside in colder temperatures or insist upon masks, even in your home. We’ve still got a long way to go before we can declare victory over the novel coronavirus, but at least we know more now than we did six months ago. And you don’t have to sanitize your apples anymore.
Source: Surfaces vs Airborne: What We Know Now About Covid-19 Transmission
2. Why fit, healthy women are the most at risk of long Covid
- At first, it all seemed so clear-cut. Some – a small minority – suffered severe symptoms. Older people, those with other health problems and, intriguingly, men were more at risk. But the overwhelming majority of those struck by C19 would experience only ‘a mild illness’.
- Now, almost nine months since the virus first hit Britain, a far more complex picture is beginning to emerge. While officials say the infection lasts about two weeks for most people, thousands of corona survivors are reporting a long-lasting, debilitating illness.
- Many Covid ‘long-haulers’, as they describe themselves, have faced a relentless battle – and symptoms are wide-ranging: crushing fatigue and breathing problems, palpitations, horrific headaches and brain fog, muscle pain, nausea, even hair loss, to name just a few.
- Many say they suffered only mildly to begin with at least – and they appear to be, on average, much younger than those admitted to hospital.
- The latest data also tells us something far more striking: they are overwhelmingly more likely to be women. This newspaper was among the first to report on the Long Covid phenomenon, back in May.
- At the time, the lung doctor who treated Prime Minister Boris Johnson, Professor Nicholas Hart, said coronavirus could end up becoming ‘this generation’s polio’ and lead to a wave of further health problems for patients many months, or years, after their symptoms begin.
- The polio epidemics of the 1950s killed thousands and left a generation with life-long mobility problems. Also a virus, it spread via bodily fluids and infected up to 8,000 people a year in the UK between 1947 and 1956, when a vaccine was finally found.
- Now Professor Tim Spector, a genetics expert at King’s College London, says information collected from 4.2 million users of his Covid Symptom Study app reveal that as many as 60,000 people in the UK are now living with effects lasting more than three months, with long-term problems ‘around twice as common in females as males’.
- The revelation is backed by further research in the US and Ireland, with one study in New York suggesting that as many as 80 per cent of those with enduring symptoms are female, while support groups such as Long Covid SOS are populated mostly by women.
- But the science remains unclear.
- Dr David Putrino, director of rehabilitation innovation at New York’s Mount Sinai hospital, has been tracking a group of patients referred to hospital during the crisis but who weren’t ill enough to be admitted. ‘Our data suggests it’s primarily women [who have long-term symptoms] – about 80 per cent,’ he says.
- They’re also relatively young, fit and healthy, he adds, with an average age of 43. About a third were athletes or had run marathons.
- It’s a conundrum – why were these women struggling to fight off the virus?
- Dr Putrino is in early discussions with Dr Akiko Iwasaki, an immunologist at Yale University, whose research has pointed to the immune system as a possible culprit.
- Dr Iwasaki has found that women whose immune systems react strongly to the virus were more likely to have longer-term difficulties. Why that is remains unclear.
- What is already known is that female immune systems are more robust than men’s.
- Inside the nucleus of every cell, DNA is packaged into thread-like structures called chromosomes. These contain sequences of ‘code’ called genes, which determine how cells function and, as a result, everything from hair and eye colour to blood type.
- The usual number of chromosomes in every cell in the body is 46 – or 23 pairs. We inherit half from our mother and half from our father. One pair of these is sex chromosomes – they determine whether a person is born male or female.
- Sex chromosomes in men and women differ in structure: women have two that are, when looked at under an extremely powerful microscope, shaped like an X. Men have one shaped like an X and one like a Y.
- A number of key immune genes are located on the X chromosome – hence women are often better equipped to fight off infection.
- It’s also believed that the female sex hormones oestrogen and progesterone help to boost the immune response and reduce inflammation.
- Studies show that women consistently produce twice as many antibodies to flu vaccines, for example. But this is a double-edged sword, according to Professor Philip Goulder, an immunologist at the University of Oxford.
- A robust immune system can cause collateral damage, he says, as well as leaving women overwhelmingly more susceptible to autoimmune conditions – diseases such as multiple sclerosis, lupus and rheumatoid arthritis – in which the immune system mistakenly turns on and attacks the body’s own healthy tissues.
- This might partly explain what is going on in Long Covid, say experts.
- What started off as a low-grade fever turned into 11 weeks of laryngitis, chest pains and a prolonged cough
- Another piece of the jigsaw comes, perhaps, from the link between Long Covid and chronic fatigue. Prof Spector’s data shows that 98 per cent of those with extended symptoms suffer from fatigue.
- Parallels can be drawn between conditions such as chronic fatigue syndrome (CFS) and ME, which both cause extreme tiredness, and Long Covid.
- Many cases of CFS and ME emerge following viral infection. And they share similarities with autoimmune conditions in that they are most common in women and involve inflammation in the body.
- Research will now investigate the links between Long Covid and CFS, and whether there are genetic similarities in those who develop either.
- The study is being led by Dr David Strain, senior clinical lecturer at the University of Exeter and co-chairman of the British Medical Association’s medical academic committee, who runs a CFS clinic.
- ‘Looking at our referral patterns, more women are attending with symptoms of CFS they’re attributing to having had Covid,’ he says. ‘But we don’t know if they’re just more likely to come forward than men, which is true of many other chronic health problems.’
- Dr Strain suggests that coronavirus might affect the mitochondria – the powerhouse of cells that supplies them with energy.
- And, crucially, this is more likely to impact women than men, since women have fewer mitochondria in their cells, and therefore have less in reserve when they are attacked.
- In the meantime, Prof Spector’s data suggests that a specific cluster of symptoms in the first week of infection could indicate an increased risk.
- He said: ‘If you’ve got a persistent cough, hoarse voice, headache, diarrhoea, you skip meals and get shortness of breath in the first week, you are two to three times more likely to get longer-term symptoms.’
- Interestingly, this list does not include a fever or loss of taste and smell, both considered key indicators of a C19 infection. It isn’t clear why, but is likely to be linked to the body’s immune response.
- What those still suffering want now is two-fold.
- Firstly, to be counted as victims of the crisis. And secondly, to warn the young and healthy that a mild illness could still result in longer-term ill health.
- Dr Alwan says: ‘Death and ICU admission are not the only bad outcomes.
- ‘So-called mild Covid results in thousands of previously healthy folk not being able to do daily activities or work for months. It’s an issue that can no longer be ignored.’
Source: Why fit, healthy women are the most at risk of long Covid
3. An ‘uncoordinated’ immune response may explain why C19 strikes some hard, particularly the elderly
- Even a world-class orchestra will produce a cacophony if its strings, woodwinds, brass, and percussion sections don’t play in harmony. Similarly, the sophisticated human immune system can fail to beat back a pathogen if its many players don’t hit the right notes at the right times. A new study now finds that people who suffer the most from C19 have an immune response that’s out of sync.
- The results help clarify how the disease progresses and could possibly inform how best to use various treatments and how to design the most effective vaccines. “We need to know exactly how the immune response is shaped to this virus,” says Donna Farber, an immunologist at Columbia University who was not involved in the research. “This is probably the most comprehensive analysis of virus-specific immunity in people who either had COVID or are acutely infected.”
- The new study, published online today in Cell, focuses on three of the most powerful arms of the adaptive immune response, the secondary defenses the body raises after the immune system’s sentinels first detect an infection. “This appears to be a virus [against which] all three arms can work together and to some extent compensate for each other,” says immunologist Shane Crotty of the La Jolla Institute for Immunology, who led the study with co-worker Alessandro Sette. “In general, if you had a response with all three, you tended to do well. People ended up running into trouble when they didn’t have a coordinated adaptive immune response.”
- When the body detects a novel virus, “innate” defensive cells—which broadly attack any pathogen—rally immediately. They also release chemical messengers called cytokines to alert other immune cells. The adaptive response, which targets the specific invader—in the case of C19, the coronavirus dubbed SARS-CoV-2—then builds over the following days. One adaptive arm consists of antibodies that aim to attach to and “neutralize” the virus. If the antibodies fail, killer T cells act as a backup, identifying and destroying any infected cells. The third arm, helper T cells, are the conductors that coordinate production of antibodies, killer T cells, and the rest of the immune orchestra.
- Crotty, Sette, and colleagues analyzed the blood of 24 people whose C19 cases ranged from mild to ultimately fatal. The researchers compared their immune responses with those of 26 others who had recovered from the disease and with a control group, 65 people who had never been infected with the virus. The study participants ranged from 20 to 86 years old. Crotty calls the study “exploratory” because he would like to conduct the same analyses in hundreds of people sick with or recovered from C19. Still, the team made several discoveries. Neutralizing antibody levels did not correlate with severity of disease, they found, and patients with the worst cases of C19 had low levels of helper and killer T cells. “It looks like T cells play a more important role than antibodies during natural infection,” Crotty says.
- Blood samples from the 10 study participants with active infections who were age 65 and older showed they were far more likely than younger infected people to have “uncoordinated” responses between the antibodies and the two T cells arms—the antibodies might have risen to high levels while one of the cellular responses remained weak, for example. This older group also had smaller populations of the “naïve” T cells that can recognize new invaders and then develop into the mature killer and helper cells capable of mounting a coordinated attack against SARS-CoV-2.
- Scientists are still debating the mechanics of the “storm” of cytokines released by innate immune cells that contribute to the severity of C19, but the new study may explain how it occurs in at least some cases. “If you kick off an innate and adaptive immune response pretty quickly, you’re going to be fine,” Crotty says. But if there’s a deficit of the adaptive arm’s T cells, the antibody response and cytokines by themselves often have trouble containing SARS-CoV-2, allowing the virus to grow to high levels. The innate system responds by pumping out still more cytokines. “Maybe the virus gets so far ahead in those people that it’s too late for the adaptive immune system to catch up,” he says.
- Studies have convincingly shown that corticosteroids like dexamethasone, which broadly dampen the immune response, can save some people who have severe disease. Crotty cautions that if clinicians give steroids too early, “you could really shoot yourself in the foot because this might be somebody whose adaptive immune response is just getting going.”
- In theory, the type of analyses done in this study may help clinicians better determine when to use these drugs. “You can assess patients based on their adaptive immunity profile,” Farber says. “This is really important.” But she also cautions that the blood may not reflect the immune responses in tissues such as the lungs, which is a key site of attack by the virus. “I don’t know if monitoring the blood is going to tell us what is going to prevent a mild case from becoming severe,” says Farber, who studies lung and airway immunity.
- Julie McElrath, who heads the vaccine and infectious disease division of the Fred Hutchinson Cancer Research Center, says these “interesting findings” might also help steer C19 vaccinemakers to concentrate more on T cell responses. Most C19 vaccines contain different versions of the surface protein spike of SARS-CoV-2. Researchers hope these vaccines will teach the body to thwart infections by making neutralizing antibodies against it. But it’s a tall order for vaccines to prevent infection completely; indeed, most of the vaccine efficacy trials primarily are evaluating protection from disease rather than infection itself.
- If viruses do slip by antibodies, T cells will be needed to mop them up. “Eliciting both antibody and T cell responses with vaccines is likely an important step to achieving efficacy against severe C19,” McElrath says. But she notes that some of the vaccine efficacy trials aren’t designed to even analyze T cell levels. And training an immune system to make strong T cell responses against SARS-CoV-2 ultimately may require using more parts of the virus in a vaccine than the spike protein alone.
- Crotty notes that there are practical challenges to measuring T cell responses, which are more difficult to assess than antibody levels. But if the vaccines being tested now prove not to work well, expect far more intensive efforts to measure and boost T cell responses. “If you can have a vaccine that has fantastic neutralizing antibodies and can sustain them, that really will be the big winner,” he says. “But if the virus slips through, our data indicate that these T cell responses are probably really important—and probably even more important the older you are.”
4. ‘A Very Serious Situation’: WHO Says Coronavirus Cases Are Rising In Europe Again
- The World Health Organization warned on Thursday that weekly coronavirus case numbers are rising in Europe at a higher rate than during the pandemic’s peak in March.
- At a virtual news conference, Dr. Hans Kluge, regional director of WHO in Europe, warned, “We do have a very serious situation unfolding before us.”
- “Weekly cases have exceeded those reported when the pandemic first peaked in Europe in March,” he said. “Last week, the region’s weekly tally exceeded 300,000 patients.”
- Wearing a green face mask, Kluge said, “Strict lockdown measures in the spring and early summer yielded good results. Our efforts, our sacrifices paid off. In June, cases hit an all-time low.”
- Reported cases in Spain, France and the U.K. were in the hundreds in June and July.
- However, Kluge said the early September case numbers “should serve as a wake-up call for all of us.” He said the numbers reflect more comprehensive testing but also “alarming rates of transmission across the region.”
- “More than half of European countries have reported a greater than 10% increase in cases in the past two weeks,” said Kluge. “Of those, seven countries have seen newly reported cases increase more than twofold in the same period.”
- “Where the pandemic goes from here is in our hands. … We have fought it back before, and we can fight back again,” he said.
- Kluge said quarantines should remain in place.
- So far, Europe has seen 4,893,614 confirmed cases, and the death toll is at 216,005 during this pandemic. Spain has the highest number of confirmed coronavirus infections in Europe at 625,651, followed by France at 454,099, the United Kingdom at 384,075 and Italy at 293,025, according to the Johns Hopkins University dashboard.
Source: Europe Is Fighting A 2nd Wave Of Coronavirus Pandemic
F. Back to School!?
1. As schools spend big on temperature check tech, experts warn: It won’t work
- The back-to-school preparations at the Sharyland Independent School District in southern Texas this year include a variety of supplies now common in daily life during the pandemic: plastic dividers, masks and hand sanitizer.
- They also include something not as common: body temperature screening terminals.
- The district, which serves about 10,200 students across 13 campuses, spent more than $178,000 on 52 walk-through infrared temperature scanners from SafeCheck USA, a Miami-based company that launched about six months ago. The school district made the purchase without testing the technology after watching a demonstration over Zoom, Assistant Superintendent Ismael Gonzalez said.
- “We are looking forward to reopening our schools. We miss our students,” he said, noting that the school district had been “flooded” with pitches for new C19 mitigation tools.
- Body temperature checks have emerged in recent months as one of the more advanced and passive coronavirus mitigation techniques, with tripods mounting infrared cameras now a common sight at the entrances of buildings.
- But just how well temperature checks work remains unclear, and epidemiologists caution that mass temperature screening systems do little to detect people infected with the coronavirus and that they could make people less safe by giving the false impression that C19 is not present.
- “In the context of schools, fever screening is a particularly bad idea,” said Katelyn Gostic, an epidemiologist at the University of Chicago, who studies the use of symptom screening systems for catching infectious diseases.
- “Fever screening only works if you have a fever. And we know that a lot of infections in children and young people seem to be asymptomatic or mild enough that you might not have a fever for several days, even though you’re contagious, or you might never develop a fever at all,” Gostic said.
- That has not stopped companies, many newly formed or with little track record in temperature detection technology, to join in the rush to pitch lucrative contracts to schools, offering fever checks, contact tracing and other safety services. A handful of companies have pivoted from selling gun detection systems to selling temperature screening systems to meet demand and prevent the spread of the coronavirus on school campuses.
- Many of the systems being marketed to schools are not vetted by the Food and Drug Administration — the agency relaxed its rules in April to allow broader use of devices for temperature screening — nor independently tested as being accurate at detecting fevers, let alone symptoms that arise from C19. Yet school districts across the country are spending hundreds of thousands of dollars, often using funds from the Coronavirus Aid, Relief and Economic Security Act, or the CARES Act, on the systems in the hope that they will help mitigate the spread of the virus.
- SafeCheck USA’s co-founder William Kakon did not respond to questions about the experts’ concerns over the technology’s accuracy. He said the system had been tested by third parties but declined to provide details.
- Other school districts have also spent considerable amounts of money on similar systems.
- In the Dothan City School District in Alabama, administrators opted to buy 23 fever screening systems for a total of $400,000, which are being set up at the entrances of the district’s 17 campuses serving around 8,000 students. The district made the purchase before testing the systems, said acting Superintendent Dennis Coe, the district’s chief operations officer.
- The school board of Fayette County in Georgia was reported to have approved the purchase of up to 75 temperature check cameras made by Hikvision — a Chinese company the Trump administration placed on a trade blacklist in October for its role in the surveillance of China’s Muslim minority — for up to $525,000. Elsewhere in Alabama, the Baldwin County School District spent nearly $1 million to buy 144 Hikvision cameras, NBC affiliate WPMI of Mobile reported.
- The appeal, said Shawn Van Scoy, the superintendent of the Gananda Central School District in New York, is preventing congestion at the start of the day. The Gananda district also bought a set of Hikvision cameras to screen for fevers.
- “Everything is cumbersome when we are trying to get a thousand kids in school in the morning,” Van Scoy said. “This will allow us to assess 40 students every minute as they enter the doors of our building.”
- The SafeCheck USA devices bought by the Sharyland schools have two infrared sensors that the company said can read the temperatures of up to 70 people per minute. Kakon said in an interview that the company sold its devices to almost 100 schools in the United States.
- Whether it’s infrared walk-through sensors or thermal cameras, the technology does the same thing, said David Pascoe, a professor emeritus of kinesiology at the University of Auburn, who served as director of the Thermal and Infrared Imaging Lab and as a U.S. delegate to the International Organization for Standardization for pandemic screening.
- “They’re all the same. You’re looking at the infrared spectrum of temperature that’s being radiated from the body,” Pascoe said, adding that it is possible to get a good temperature reading of someone using the systems but that the way the reading is done has to be in line with international standards to be effective. That means scanning people one at a time after they’ve had enough time to regulate their temperature from outside and getting a good reading of each person’s face, preferably while practicing physical distancing, so a tall person doesn’t block the face of a shorter person.
- Scanning large numbers of people every minute, he said, is less likely to produce accurate temperature readings.
- “This is no different than having a fake camera in the building and people have the illusion that they’re safe and they let their guard down,” he said.
- Other schools have bought Feevr thermal cameras from Los Angeles-based technology startup X.Labs, which until March specialized in selling thermal cameras for detecting concealed weapons. The Kershaw County School District in South Carolina bought 20 Feevr cameras for about $75,000 to check its 10,000 students for C19 symptoms, while the Van Vleck Independent School District in Texas bought three cameras for about $10,000.
- Feevr uses the Flir One thermal camera, which attaches to a smartphone. Flir Systems promotes the model, which costs from $299, to electricians and mechanics to identify hot spots in machinery. According to Flir, the camera is not sensitive enough for accurately checking human skin temperature.
- X.Labs said it developed its own software to improve the performance of Flir’s entry-level cameras.
- X.Labs said students entering buildings must wait 90 to 120 seconds before Feevr can accurately estimate body temperature — and longer if they’ve been in direct sunlight or exercising.
- Asked whether Feevr devices detected fevers, as indicated by the product’s name and early marketing materials, X.Labs co-founder Todd Dunphy responded: “No.”
- Sam Skinner, chief experience officer at X.Labs, said, “It’s a screening mechanism to determine whether or not a person has elevated skin temperature, and skin temperature is actually not related to febrile conditions.”
- Dunphy said that X.Labs developed Feevr at the request of customers who already used its gun detection technology but acknowledged that half of people with C19 are asymptomatic and that he didn’t think Feevr would be a “big part of our business going forward,” even though “hundreds” of clients have bought into the system.
- Some of the more established vendors of security products to schools, including Axis Communications, have avoided the fever detection business altogether over concerns that thermal cameras aren’t accurate enough to detect fevers quickly in large groups because of how sunshine, exertion and masks can alter readings.
- “If you have 500 students entering between 8:00 a.m. and 8:15 a.m., we don’t believe we are going to make a product work accurately enough,” said Fredrik Nilsson, vice president of the Americas at Axis Communications, a major supplier of surveillance cameras to schools, retailers and other businesses. “We are very long-term and not opportunistic.”
- He compared the proliferation of companies selling fever detection tools to those that sold facial recognition technology in the aftermath of the terrorist attacks of Sept. 11, 2001.
- “A lot of airports went out and spent hundreds of thousands of dollars to install facial recognition at check-in and realized it wasn’t accurate enough, and they had tens of thousands of false positives a day,” he said, warning that schools could find themselves in a similar predicament.
- Nilsson said there are other “tried and tested technologies that can be repurposed to have safe reopenings” — for example, using video analytics to count the number of people going in and out of a space to make sure it’s not over capacity or to create heat maps of congested areas to inform social distancing rules.
- In North Carolina, Phoenix Academy charter schools spent $10,000 on its set of three Feevr systems, which is only a small fraction of the total $250,000 the small three-school system is spending to deal with C19, said Brandon Lenoir, a spokesman for Phoenix Academy.
- “None of this is cheap. We spent a lot of money, but how do we put a price on the safety of our kids?” Lenoir said.
Source: As schools spend big on temperature check tech, experts warn: It won’t work
G. The Road Back?
1. How to Live With Covid, Not for It
Opinion by Joseph A. Ladapo, an associate professor at UCLA’s David Geffen School of Medicine.
- The battle against C19 is entering a new phase, and the choice for society is whether to live with the virus or to live for it. This new phase has been marked by four developments: Many states have weathered post-shutdown outbreaks and case counts are falling; the percentage of Americans saying the pandemic is worsening peaked in July and is trending down, according to Gallup polling; the culture wars over lockdowns and distancing mandates are cooling; and inexpensive rapid testing and a vaccine will soon be available widely. These developments create an atmosphere of possibility—and an opportunity to pivot away from the fear-fueled policy-making that has characterized the pandemic.
- Policies forged in fear and panic have wrought tremendous damage in exchange for benefits that were attainable at a much lower cost. Over the past six months, we have managed to sow vicious conflict over health mandates among people who would otherwise be cordial; erode age-old social customs, like visible smiles and human touch, which are critical to social cohesion and personal well-being; and condemn millions of Americans to financial instability, depression and even domestic violence.
- The collective goal of this new phase should be to avoid repeating the mistakes of the past. When faced in March with the choice between imposing limited shutdowns to buy hospitals time and increase capacity, and enormous, indefinite shutdowns that ignored societal and economic costs, most political leaders chose the latter. When faced in May and June with the choice between embracing policies that balanced C19 prevention with the activities that give life meaning and policies that sowed distrust and stirred fierce passions over civil liberties, most political leaders chose the latter. We have the opportunity to choose differently this time.
- Some signs point toward institutions shifting away from fear-fueled decision making. The Centers for Disease Control and Prevention issued guidance last month that contacts of persons with C19 “do not necessarily” need testing if they are asymptomatic. Early testing among those infected with the virus may yield false negatives, and testing vulnerable adults and their contacts is far more valuable than testing healthy young adults. The CDC now recommends focusing tests where they are likely to yield the greatest public-health benefits.
- The good sense of this recommendation is so plain, it is almost stupefying. Where is the controversy in placing disproportionate energy and attention on populations that are disproportionately at risk for harm from C19? Residents of nursing homes and other long-term care facilities—who represent less than 1% of the U.S. population—have comprised nearly half of deaths from C19. A recent study in Annals of Internal Medicine reported that the infection fatality rate in noninstitutionalized persons under 40 was 0.01%, compared with 1.7% among people older than 60—a nearly 200-fold difference. Sensible policies focus special attention on populations facing the greatest harm.
- The criticism the CDC has received underscores the determination of too many leaders and health officials to continue choosing fear-fueled policy-making. Consider the facts: The average C19 transmission rate to close contacts is roughly 10% or 15%. The actual number of infections may be six to 24 times the number of reported cases, according to a July study in JAMA Internal Medicine. It would be impossible to close the wide gap between detected and undetected cases without resort to authoritarianism. It’s clear that testing low-risk contacts is a low-value activity.
- But critics of the CDC’s new recommendation subscribe to the belief—knowingly or not—that all attempts to stop C19 transmission are worthwhile, no matter how small the benefit or how high the cost. Increased public recognition of—and scientific support for—sensible policies will steer us away from destructive decisions fueled by fear.
- There is also an opportunity to revisit decisions about schooling made by educational institutions at every level. College administrators in Ohio are expending substantial energy trying to stop young people from socializing; high schools in Georgia are being pushed toward closure due to mass quarantining; and intricate plans are being drafted for young children—for whom the virus is less harmful than seasonal influenza—in districts such as Los Angeles.
- Placing disproportionate focus on C19 transmission in low-risk populations leads to unwise decisions that do more harm than good. A wiser investment would focus on protecting vulnerable populations, including older teachers, family members and essential employees, by directing testing and personal protective equipment to them and their close contacts. Early outpatient therapies for C19 may also prevent serious illness in these populations, as described in a recent American Journal of Medicine article.
- The CDC’s quarantine guidelines for healthy, low-risk students should be revisited in light of the outsize effect quarantines have on their educational experience—and the possibility of perpetual quarantining for exposed students if testing is performed frequently. University policies for C19 prevention also have an edge of cruelty: Many of these administrators suspending students “caught” socializing would have been doing the same 30 or 40 years ago.
- The point of life is living, and everyone is better off with policies that focus on protecting the most vulnerable populations. That doesn’t take universal rapid testing or never-ending mandates. It requires only abandoning fear, being sensible about who is targeted for testing and protections, expanding treatment capacity and therapies—and choosing to live with the virus, rather than to live for it.
Source: Opinion | How to Live With Covid, Not for It
H. Lockdowns
1. By the numbers, it’s hard to see how lockdowns saved many lives
- The New York Times describes Sweden’s approach to C19, which has been notably less restrictive than the policies adopted by other European countries and the United States, as “disastrous” and “calamitous.” By contrast, Scott Atlas, the physician and Hoover Institution fellow who is advising President Trump on the epidemic, thinks Sweden’s policy is “relatively rational” and “has been inappropriately criticized.”
- The sharp disagreement about Sweden is part of the wider debate about the cost-effectiveness of broad lockdowns as a strategy for dealing with the pandemic. While it is premature to reach firm conclusions, the evidence so far suggests that Sweden is faring better than the United States, where governors tried to contain the virus by imposing sweeping social and economic restrictions.
- Despite some early blunders (most conspicuously, the failure to adequately protect nursing-home residents), Sweden generally has tried to protect people who are at highest risk of dying from C19 while giving the rest of the population considerably more freedom than was allowed by the lockdowns that all but a few US governors imposed in the spring. That doesn’t mean Swedes carried on as usual, since the government imposed some restrictions (including a ban on large public gatherings) and issued recommendations aimed at reducing virus transmission.
- The consequences of that policy look bad if you compare Sweden to Denmark, Finland and Norway, neighboring countries that have seen far fewer C19 deaths per capita. Yet Sweden has a lower death rate than several European countries that imposed lockdowns, including Belgium, Italy, Spain and the United Kingdom.
- The US-Sweden comparison is especially striking. The US per-capita fatality rate recently surpassed Sweden’s, and the gap is growing, since the cumulative death toll is rising much faster in the United States.
- The seven-day average of daily deaths peaked around the same time last spring in both countries. Adjusted for population, the peak was higher in Sweden.
- Since then, however, that average has fallen more precipitously in Sweden — by 99% since April 16, compared with 65% in the United States since April 21. The seven-day average of newly confirmed cases also has dropped sharply in Sweden, by nearly 80% since late June.
- In America during the same period, daily new cases initially rose, an ascent that started a month and a half after states began lifting their lockdowns. The seven-day average peaked in late July and has since fallen by 46%.
- Achieving herd immunity, which protects people in high-risk groups by making it less likely that they will encounter carriers, was never an official goal of Sweden’s policy. But recent trends are consistent with the hypothesis that Sweden has achieved some measure of herd immunity via a combination of exposure to the virus, T-cell response fostered by prior exposure to other coronaviruses, and greater natural resistance among the remaining uninfected population.
- In the United States, lockdowns (despite the huge costs they entailed) have not had any obvious payoff in terms of fewer C19 deaths, although they may have changed the timing of those deaths. Perhaps the outcome would have been different if lockdowns had been imposed earlier or if they had been lifted later and more cautiously. But perhaps not.
- In a National Bureau of Economic Research paper published last month, UCLA economist Andrew Atkeson and two other researchers, after looking at C19 trends in 23 countries and 25 US states that had seen more than 1,000 deaths from the disease by late July, found little evidence that variations in policy explain the course of the epidemic in different places.
- Atkeson & Co. conclude that the role of legal restrictions “is likely overstated,” saying their findings “raise doubt about the importance” of lockdowns in controlling the epidemic. It would not be the first time people have exaggerated the potency of government action while ignoring everything else.
Source: By the numbers, it’s hard to see how lockdowns saved many lives
I. Projections & Our (Possible) Future
1. A Military-Funded Biosensor Could Be the Future of Pandemic Detection
If it wins FDA approval next year, the two-part sensor could help spot new infections weeks before symptoms begin to show
- Why are pandemics so hard to stop? Often it’s because the disease moves faster than people can be tested for it. The Defense Department is helping to fund a new study to determine whether an under-the-skin biosensor can help trackers keep up — by detecting flu-like infections even before their symptoms begin to show. Its maker, Profusa, says the sensor is on track to try for FDA approval by early next year.
- The sensor has two parts. One is a 3mm string of hydrogel, a material whose network of polymer chains is used in some contact lenses and other implants. Inserted under the skin with a syringe, the string includes a specially engineered molecule that sends a fluorescent signal outside of the body when the body begins to fight an infection. The other part is an electronic component attached to the skin. It sends light through the skin, detects the fluorescent signal and generates another signal that the wearer can send to a doctor, website, etc. It’s like a blood lab on the skin that can pick up the body’s response to illness before the presence of other symptoms, like coughing.
- Profusa’s newest funded study will test how well the sensor can detect influenza outbreaks up to three weeks before it’s possible to detect them using current methods.
- Hwang said his company has received grants from the Defense Advanced Research Projects Agency, or DARPA, since around 2011. “They gave us grant money to help our research and as we prove out a certain milestone, as we de-risk the technology, they give us a second phrase and a third phase and provide support,” he said. “Their support has transitioned from grants into these types of programs that create real-world evidence.”
Source: A Military-Funded Biosensor Could Be the Future of Pandemic Detection
J. Practical Tips & Other Useful Information
1. The Odds of Catching Covid on a Flight Are Slim
- If you decide to fly, the odds that you will pick up C19 are low, according to one expert analysis. Despite the known dangers of crowded, enclosed spaces, planes have not been the sites of so-called superspreading events, at least so far.
- That’s not to say flying is perfectly safe — safety is relative and subjective. But as restrictions continue to change, the only way to move forward through this long pandemic is to start thinking in terms of risk-benefit ratios. Very little is without risk, but perhaps some risks — such as flying — are small enough to warrant taking.
- Arnold Barnett, a professor of management science at the Massachusetts Institute of Technology, has been trying to quantify the odds of catching C19 from flying. He’s factored in a bunch of variables, including the odds of being seated near someone in the infectious stage of the disease, and the odds that the protection of masks (now required on most flights) will fail. He’s accounted for the way air is constantly renewed in airplane cabins, which experts say makes it very unlikely you’ll contract the disease from people who aren’t in your immediate vicinity — your row, or, to a lesser extent, the person across the aisle, the people ahead of you or the people behind you.
- What Barnett came up with was that we have about a 1/4300 chance of getting C19 on a full 2-hour flight — that is, about 1 in 4300 passengers will pick up the virus, on average. The odds of getting the virus are about half that, 1/7700, if airlines leave the middle seat empty. He’s posted his results as a not-yet-peer-reviewed preprint.
- The odds of dying of a case contracted in flight, he found, are even lower — between 1 in 400,000 and 1 in 600,000 — depending on your age and other risk factors. To put that in perspective, those odds are comparable to the average risk of getting a fatal case in a typical two hours on the ground.
- The numbers all sound low enough, though Barnett says they are still high compared to the 1 in 34 million odds your flight will end in a deadly crash. He told me he wouldn’t fly right now because his age, 72, puts him at higher risk than the average American, and he says you have to consider the risk of adding to the problem by getting the virus and unknowingly passing it on to others.
- Other experts have been mixed on whether they, personally, would fly. The Boston Globe recently reported that of 15 epidemiologists and infectious disease experts surveyed, 13 said they would not fly at this time — however it wasn’t clear whether they had any reason to get on a plane.
- University of Massachusetts biology professor Erin Bromage says he is flying every week, as he advises federal, state and district courts on how to reopen while minimizing risks. Whereas many experts are taking a zero-tolerance for risk approach, he’s trying to find a middle ground — and helping others do it in a rational way.
- Drawing on a background in industrial mechanics and pilot training (an injury forced him to switch career paths into biology), Bromage says that the air exchange system in planes is better than in hospitals, with the air in the cabin being completely replaced 30 times every hour. He agrees with MIT’s Barnett, though, that it’s possible to transmit the disease to or from your close neighbors.
- He and Barnett both suggested that customers should, if possible, choose an airline, such as Jet Blue, that promises to keep the middle seat open. That cuts way back on the odds of getting or giving the virus. JetBlue also promises that solo travelers won’t have a neighbor in a two-seat row.
- Real-world data bodes well for flying, too. Australia has been using contact tracing to investigate Covid transmission on hundreds of flights, and has found that while infected people got on planes, nobody got infected on a plane. Worldwide, there have been a couple of individual transmissions possibly linked to flights, but no superspreading-type events.
- Assuming we’ll be living with this disease for months to come, we will need ways to separate low-risk activities from high-risk ones. Keeping informed of relative risks can help us do that. By worrying less about the relatively safer part of a trip — the actual flight — we can pay more attention to the potentially riskier parts, such as crowds and tightly packed lines at the airport.
- Of course, we’re all obligated to avoid adding to the spread of the disease, and this means taking precautions in the air, such as wearing a mask and staying home if sick, and keeping a distance from others at the airport.
- What happens at your destination matters too. Traveling around and mingling with distant contacts can increase the risk of spreading the virus more than mingling with a comparable number of people closer to home. So people can help themselves and others by driving their own cars to the airport and renting cars wherever they arrive, rather than taking taxis or ride-shares.
- In the old normal, Bromage would wrap up his advisory duties and have dinner with the people he’s working with. Now, he just goes back to his hotel room. “It’s quite lonely,” he says. Like so much this year, it’s a compromise.
Source: Is It Safe to Fly? Here Are the Odds of Catching Covid on a Plane
K. Johns Hopkins COVID-19 Update
September 18, 2020
1. Numbers & Trends (Overview)
- The WHO COVID-19 Dashboard reports 30.06 million cases and 943,433 deaths as of 10:00am EDT on September 18. This week appears to be on pace to set a new record for weekly incidence—currently at 315,919 cases. As the cumulative global incidence surpasses 30 million, the following timeline will provide some context for the trajectory of the C19 pandemic:
- 1 case to 1 million cases: 90 days
- 1 million to 5 million: 48 days
- 5 million to 10 million: 38 days
- 10 million to 20 million: 44 days
- 20 million to 30 million: 37 days
- The global daily incidence is once again increasing, driven largely by increasing incidence in India and multiple countries in Europe. After leveling off at approximately 260,000 new cases per day, the global daily average is now up to 285,000. As expected, the daily incidence in Asia and Europe are increasing, while North and South America appear to have plateaued or started to decline. Africa’s daily incidence peaked in mid-to-late June, and it has steadily decreased since then, now reporting fewer than 7,500 new cases per day for the entire continent. Proportionately, Asia’s and Europe’s contribution to the global daily incidence are increasing, while North and South America’s and Africa’s are decreasing. In fact, Asia currently accounts for more than 40% of the total daily incidence. On a per capita basis, South America still leads all continents at 140 daily cases per million population, followed by North America (84 per million) and Europe (58 per million). The global average is 37 daily cases per million population.
- With respect to deaths, Asia and North and South America are all reporting similar daily mortality (1,350-1,800 deaths per day), and Africa, Europe, and Oceania are all reporting fewer than 500 deaths per day. On a per capita basis, South America (3.4 daily deaths per million population) and North America (2.2 per million) are both reporting higher than the global average (0.7 per million). Europe (0.6 per million) is near the global average, and Africa, Asia, and Oceania are all reporting fewer than 0.4 daily deaths per million population.
- The US represents 22% of the cumulative global cases and 21% of the deaths, despite accounting for 4.25% of the global population.
2. UNITED STATES
- The US CDC reported 6.61 million total cases and 196,277 deaths. The US is averaging 38,538 new cases and 859 deaths per day. The average daily incidence has increased by 11% over the last 3 days, and daily mortality has increased by 17% over the last 4 days. It is possible that these increases represent a reversion to the expected average after lower reporting over the Labor Day holiday weekend, but we will continue to monitor the situation to determine if it is the beginning of longer-term trends. If the US continues at its current pace, it could reach 200,000 cumulative C19 deaths by Tuesday’s update.
- In total, 21 states (no change) are reporting more than 100,000 cases, including California with more than 700,000 cases; Florida and Texas with more than 600,000; New York with more than 400,000; and Arizona, Georgia, and Illinois with more than 200,000. The Georgia Department of Health is reporting 300,903 cumulative cases, so we expect this to be reflected in the next CDC update.
- The Johns Hopkins CSSE dashboard reported 6.69 million US cases and 198,055 deaths as of 1:30pm EDT on September 18.
3. EUROPE
- The WHO offered a stark warning for Europe as C19 incidence continues to increase. Last week, incidence in Europe exceeded the continent’s first peak in March, and the epidemic continues to grow. While the resurgence of the virus is spread across the continent, rather than located in a few countries or regions with high transmission, the recent trend is concerning. The rise in European C19 incidence has been driven, in part, by individuals aged 25-49. One potential change that could be affecting this increase is a shift in countries’ approach to containing their respective epidemics. A number of European countries have modified their approach from combatting the virus to coexistence. For example, French President Emmanuel Macron and Italian Minister of Health Roberto Speranza that emphasize that the public needs to learn how to “live with the virus.”
4. UNITED KINGDOM
- The UK continues to struggle with SARS-CoV-2 testing capacity. The national laboratory network was not prepared to handle the surge in testing demand that coincided with children returning to school, and the UK testing program was forced to send tests to France and Germany in order to increase capacity. Following reports of a national backlog of 185,000 tests that is delaying results and hindering the public health response, UK Prime Minister Boris Johnson unveiled a plan dubbed Operation Moonshot, which aims to scale up national testing capacity to 10 million people a day by early 2021. This capacity could effectively allow everyone in the UK to be tested weekly. In light of a series of failures or missteps in the UK testing program—a situation in which the UK is not alone—experts question the feasibility of scaling up testing to this volume. Notably, the kind of rapid tests needed to realize this vision are still not widely available, nor are they approved for use in the UK.
- Like most countries, the UK has felt serious economic consequences from the C19 pandemic and its corresponding impact on routine social and economic activity. The country’s unemployment rate is now the highest it has been in the past 2 years, and the 16-24 age group is facing the most severe decrease in employment. Like many schools in the US and elsewhere, colleges and universities in the UK have resumed fall classes. And like we have reported in the US, some schools are implementing harsh punishments for students who violate C19 policies. For example, Trinity College Cambridge came under some scrutiny after announcing that it would evict students from university housing if they are involved in a C19 outbreak. In addition to the effects on students who may not have alternate housing, this approach disincentivizes reporting by students, which could allow outbreaks to go undetected. If students are afraid to report symptoms or suspected cases, it could facilitate transmission both on campus and in the local community.
5. INDIA
- reported nearly 100,000 new C19 cases, continuing to set new records for daily incidence, and it is currently reporting more than 1 million active cases nationwide. At this pace, India will soon surpass the US as #1 globally in terms of cumulative C19 incidence. In addition to the national incidence, incidence is also increasing in major cities, including Mumbai and New Delhi, after a temporary plateau. India is testing more than 1 million samples a day. While this is a large number, it is unfortunately low on a per capita and per case basis. There are concerns over whether the country will be able to meaningfully slow the transmission of SARS-CoV-2, and questions about how much of the population may have already had the disease. The Times of India reported that serological studies have identified some communities with high seropositivity, including some greater than 50%. One study estimates that as many as 25% of the population nationwide have been infected. While some health and government officials have estimated that herd immunity could be observed at 60-70% seropositivity, it is unclear how accurate this estimate is. Additionally, there are considerable differences in seropositivity between communities, and the presence of antibodies does not necessarily mean that an individual is immune from infection. Regardless, India’s national trends suggest that its epidemic continues to accelerate.
6. INDONESIA
- Indonesia’s C19 epidemic has surged over the past several weeks, with daily incidence increasing more than 80% since August 25. In order to address the growing epidemic, some Indonesian officials are using unique approaches to increase adherence to policies, including mask use. In the Cerme district in East Java, the local government reportedly forced 8 individuals to dig graves for C19 victims as punishment for violating the local mask mandate. The district is experiencing a shortage of grave diggers, and the district’s leadership believed that the punishment could both fill that role temporarily and serve as a deterrent to others. Notably, the individuals did not participate in any burial services and did not have contact with the bodies of any C19 victim. And in Jakarta, the local government reportedly ”paraded” coffins containing dummies wearing masks through the city and displayed them in various public locations to serve as a stark reminder to wear a mask. The effort was met with considerable criticism and opposition by the public, some of whom cited the government’s failure to effectively implement social distancing and quarantine policies and delays in distributing economic and social assistance to the public.
7. VACCINE ESPIONAGE
- As governments and countries press ahead with efforts to develop their own SARS-CoV-2 vaccine—as opposed to large, collaborative, multilateral efforts—”vaccine nationalism” not only creates challenges for the equitable global availability of a future vaccine, it also provides incentive for increased foreign intrusion and “espionage targeting vaccine research and development.” According to analysis published by the Council on Foreign Relations, espionage (including cyber espionage) is not technically prohibited under international law; however, it would violate international law if it were to result in “significant adverse or harmful consequences.” The analysis highlights the “ubiquity of cyber espionage” on SAR-CoV-2 vaccine efforts and the difficulty in “defending against or deterring” it.
- A previous report by The New York Times indicates that Chinese intelligence operatives conducted cyber espionage on academic research institutions working on SARS-CoV-2 vaccines, rather than pharmaceutical companies, and leveraged information from the WHO to direct their activities. Additionally, Russian and Iranian intelligence organizations “targeted vaccine research networks” in multiple countries, including in Canada, the UK, and the US. In July, the US Department of Justice charged 2 Chinese nationals with spying on multiple US entities conducting SARS-CoV-2 vaccine research—including Moderna Therapeutics, which is currently conducting late-stage clinical trials for its vaccine candidate—and entities in multiple other countries.
8. DOWNSTREAM IMPACTS: GLOBAL HEALTH
- The Bill and Melinda Gates Foundation released a report that assesses the progress made and outstanding gaps in terms of achieving the Sustainable Development Goals (SDGs). The SDGs were established in 2015 as a follow-on to the Millennium Development Goals, with the goal of ending poverty, reducing inequality, and stopping climate change by 2030. The Gates Foundation report notes that, while progress has been made each year since the establishment of the SDGs, that progress largely stopped in 2020, primarily as a direct result of the C19 pandemic. Additionally, the report notes that efforts to establish strong vaccine coverage have been severely affected, commenting that vaccination has been “set back about 25 years in about 25 weeks.” The severe global recession has driven much of the regression in 2020, particularly in lower-income countries that are largely reliant on informal economies. Women are especially affected. Additionally, the pandemic response has reduced the amount of funding available from governments, both for domestic populations and international aid, which further limits aid available to the public. The report indicates that 68 million people in lower-middle-income countries have been forced into poverty as a result of the pandemic and that an additional 37 million people have been forced into extreme poverty worldwide.
9. VIRTUAL UN GENERAL ASSEMBLY
- In July, the UN announced that the 75th UN General Assembly would largely be held virtually, with Member States and others participating remotely via videoconference and pre-recorded video statements. UN Secretary-General Antonia Guterres acknowledged that the virtual solution is far from ideal, and he expects a “huge loss in the efficiency of diplomacy” resulting from the virtual format. As with many international and diplomatic fora, much of the important and interesting work at the General Assembly occurs outside of formal meetings, which is considerably more difficult if relevant parties are unable to have face-to-face conversations. Notably, the option to deliver statements via video has resulted in increased participation by heads of state, particularly by those who do not typically attend the General Assembly in New York. The annual meeting commenced earlier this week, and is scheduled to continue through October 2. In addition to a virtual General Debate, other high-profile events—including on Sustainable Development Goals, biodiversity, women’s rights, and the commemoration of the UN’s 75th anniversary—will also be held virtually.
10. PREGNANT WOMEN MORBIDITY & MORTALITY
- Researchers from the C19-Associated Hospitalization Surveillance Network (COVID-NET) published findings from a study on C19 in pregnant women. The study, published in the US CDC’s MMWR, involved 598 hospitalized pregnant women with confirmed SARS-CoV-2 infection. The patients included women in all 3 trimesters of pregnancy, but 87.4% were hospitalized during the third trimester. Notably, 81.9% of those admitted during the third trimester were hospitalized for “obstetric indications” (eg, labor and delivery).
- Among 458 women who had completed pregnancy at the time of their discharge, 97.8% resulted in a live birth. Pregnancy losses occurred in both symptomatic and asymptomatic patients. Among live births, 12.6% were pre-term, including 23.1% of live births among symptomatic patients and 8.0% among asymptomatic patients. The overall prevalence of pre-term births in 2010 was 10%, which suggests that pregnant C19 patients could potentially be at elevated risk for pre-term birth. Additionally, 2 live births died shortly after delivery, and both were born to symptomatic patients who required mechanical ventilation. From March-August, an estimated 25% of hospitalized women aged 15-49 with confirmed SARS-CoV-2 infection were pregnant, compared to an estimated 5% in the general population. The study was not designed to determine the significance of these findings, but the results indicate that pregnant women could be at elevated risk for SARS-CoV-2-related complications and that additional research should be conducted to better characterize the effects of SARS-CoV-2 infection in pregnant women.
11. US CDC SCHOOL & CHILDCARE GUIDANCE
- The US CDC published a set of indicators to assist school officials and state and local governments in making dynamic decisions regarding how to operate schools in the midst of the US C19 epidemic. The indicators include specific thresholds for estimating the risk of SARS-CoV-2 transmission in schools. The Core Indicators include per capita C19 incidence and test positivity in the community over the past 2 weeks as well as the school’s ability to implement 5 recommended risk mitigation strategies: mask use, social distancing, enhanced hygiene and respiratory etiquette, enhanced cleaning and disinfection, and contact tracing. An additional list of Secondary Indicators address relative change in incidence, hospital bed and ICU capacity, and the existence of local C19 outbreaks. Each indicator is divided into 5 risk categories to aid school and government officials in their risk assessments.
- The guidance suggests that schools with higher assessed risk “could consider alternative learning models,” such as virtual or hybrid classes, to mitigate the risk. The guidance does not instruct school and government officials how exactly to factor these indicators into their risk assessment, but these metrics and key recommended strategies do provide additional information to inform school decision-making.
- The timing of the guidance has raised criticism of the CDC for not distributing it sooner, in time to inform school planning and preparedness efforts. Notably, many schools have been in session for weeks already, and this kind of guidance would have been more helpful as schools were developing their plans, particularly those that aimed to resume in-person classes. Analysis by Dr. Ashish Jha, Director of the Harvard Global Health Institute, found that 56% of US counties fall into the “highest” risk category and 31% in the “higher” risk category (the two highest categories), based on local C19 incidence and test positivity, which accounts for nearly 90% of the US population.
- CDC Director Dr. Robert Redfield also indicated that the CDC is developing guidance regarding asymptomatic or presymptomatic testing to screen for SARS-CoV-2 infections, including at schools, businesses, and other locations. As effective rapid tests become available, screening could provide important information to help school and health officials more quickly identify and respond to emerging outbreaks. That guidance is expected to be published in the near future.
12. US VACCINE DISTRIBUTION PLAN
- On September 16, the US CDC released guidance for jurisdictions to prepare operationally for SARS-CoV-2 mass vaccination. The document states that pandemic influenza planning activities and routine immunization preparedness efforts can serve as a foundation for SARS-CoV-2 vaccination planning; however, additional planning is necessary to undertake vaccination on scale necessary to combat the pandemic. Jurisdictions are required to submit their plans by October 16 in order to receive federal funding support. The document advises jurisdictions to test their plans and establish timelines for their preparedness efforts.
- The document describes 3 main phases to support SARS-CoV-2 mass vaccination planning efforts. Phase 1 is expected to involve an initial limited supply of vaccine, which will focus primarily on critical high-priority populations. Vaccination during Phase 1 will occur predominantly in closed points of dispensing (PODs; ie, limited to specific eligible groups). Phase 1A will prioritize healthcare workers, and Phase 1B will expand to other essential workers and individuals at high risk for severe disease and death. In Phase 2, it is expected that the available supply will be sufficient to start vaccinating the general population. The venues for vaccination would need to expand to include clinical settings, pharmacies, and public health mass vaccination clinics (eg, open PODS) and other settings. Phase 3 consists of continued vaccination and a shift to routine immunization strategies for SARS-CoV-2.
- The guidance notes that a surge in vaccine demand may be possible by Phase 2, and a broad vaccine administration network could be needed to support surge capacity. The guidance document notes several key challenges, including ensuring equitable allocation and distribution of the vaccines. Additionally, the guidance also highlights the potential that the vaccine could require an ultra-cold chain (-60 to -80°C). Ancillary kits containing some of the key supplies needed to conduct vaccination, including syringes and alcohol pads, will be sent to jurisdictions. The vaccine itself may be distributed centrally by the federal government or potentially directly from the manufacturer—such as early in the vaccination effort for vaccines requiring ultra-cold chain.
- Considerable uncertainty remains regarding the timeline for vaccine availability, so the document does not include specific timelines for each mass vaccination phase. CDC Director Dr. Robert Redfield recently stated in testimony to the US Senate that a vaccine would likely not be available for large-scale general public rollout until spring or summer of 2021. President Donald Trump directly contradicted Dr. Redfield at a press conference later that day, stating that distribution would be “rapid,” possibly starting in October, and that the military would be involved in mass vaccination efforts. The role of the military in distributing the vaccine is unclear, and some experts have raised concerns that the inclusion of military assets in vaccination could exacerbate mistrust in the federal government among certain populations, particularly communities of color. An additional concern is the lack of funding that state and local jurisdictions have to support large-scale mass vaccination, particularly considering the chronic underfunding of public health infrastructure. Dr. Redfield stated that it could take up to US$6 billion to distribute the vaccine; however, the CDC currently has approximately US$600 million to support C19 relief efforts. The funding needed to support vaccine distribution efforts have reportedly been stalled as Congress has been unable to finalize another C19 relief package.
13. US CDC TESTING GUIDANCE
- Following up on an emerging storyline regarding the potential influence of political appointees in CDC reporting and guidance, The New York Times reports that controversial SARS-CoV-2 testing guidance published on the US CDC website was not drafted by CDC experts. The guidance in question stated that individuals with known exposure to C19 cases but who are not exhibiting symptoms “do not necessarily need” to be tested. Following the update, multiple media outlets reported that the changes were influenced by pressure from White House officials, including reports that Dr. Anthony Fauci did not sign off on the changes before they were published. The new New York Times report indicates that the update was drafted by officials at the Department of Health and Human Services and the White House Coronavirus Task Force and posted to the CDC website without going through the CDC’s traditional scientific review process. According to the report, additional changes to the testing guidance are expected to be posted today; however, these changes may also be circumventing the CDC review process.