Recent Developments & Information
June 1, 2020
“Remember that reopening does not mean we’re going back to the way things were. We go forward. New York City is reopening to a new normal. People will be wearing masks, people will be socially distanced.”New York Governor Cuomo
“The Danish Health Authority continues to consider that covid-19 cannot be described as a generally dangerous disease, as it does not have either a usually serious course or a high mortality rate.”Excerpt from a leaked email exchange between Danish Health Authority and Danish Prime Minister
“The dangerousness of Covid-19 was overestimated: probably at no point did the danger posed by the new virus go beyond the normal level. The danger is obviously no greater than that of many other viruses. There is no evidence that this was more than a false alarm.”Excerpt from a leaked report commissioned by the German department of the interior
Without being melodramatic, COVID-19 is like the last nail in the coffin of globalization. The 2008-2009 crisis gave globalization a big hit, as did Brexit, as did the U.S.-China trade war, but COVID is taking it to a new level.Carmen Reinhart, incoming Chief Economist for the World Bank
Index Of Featured Stories & Links
Note: All of stories listed below are included in this Update, but we have included links to the stories upfront so that you can quickly jump to a story if you want.
- By the Numbers
- Assessing Your Risk: Fatality Rates and What Increases Your Risk of Death
- New Scientific Findings
- 10% of C19 patients with diabetes die within a week of hospitalization (!)
- The nose could be the body’s entry point to infection
- New Study Outlines a Roadmap for Effective Treatment of C19
- Potential Treatments
- Blood plasma is our best drug
- New Research Points to Treatment for C19 Cytokine Storms, Solution to Global Pandemic
- Can Alpha Blockers Ease Severe C19 Symptoms by Preventing ‘Cytokine Storm’ ?
- Novartis will start making coronavirus vaccine this month
- Big gene therapy names line up behind experimental C19 vaccine
- It’s Not Whether You’re Exposed to the Virus, But How Much
- Yikes! Saliva Droplets From Mild Cough Travel Up to 18 Feet
- Immunity to Coronaviruses: Here’s What We Know So Far
- Monkeys develop immunity to coronavirus. Can humans?
- Concerns & Unknowns
- C19 can cause debilitating long-term illness
- Many remain afraid to go to a hospital over C19 fears
- The Road Back?
- We’re Reopening Notre Dame – It’s Worth the Risk
- Practical Tips
- Flying during a Pandemic – What’s It Like and How To Reduce Risk
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- We do not endorse, and may not agree with, any opinion or view included in this Update. We include a wide spectrum of opinions and views as we believe that it gives perspective on what people are thinking and may give insights into our future.
A. Our World As Seen Through Headlines
(In No Particular Order)
- Gripped by disease, unemployment and outrage at the police, America plunges into crisis
- CDC chief defends failure to spot early coronavirus spread in U.S.
- Supreme Court, in rare late-night ruling, says California may enforce certain restrictions on religious gatherings
- All coronavirus testing centers shuttered in Los Angeles over ‘safety worries’ during protests
- From the Andes to Tibet, the coronavirus seems to be sparing populations at high altitudes
- Australian Health Authorities Urge Caution as Lockdowns Ease
- Mylan’s Pakistan Partner to Start Selling Remdesivir Within Two Months
- NY coronavirus death toll hits lowest point since March
- LA reports 2,000+ new cases
- Brazil Overtakes France, Is Now 4th in Global Covid-19 Deaths
- Spain pushes for another 2-week lockdown extension
- Global COVID-19 cases pass 6,000,000
- Russia cases pass 400,000
- Iran case total passes 150,000
- India reports record jump in new cases after extending lockdown
- China reports new asymptomatic cases tied to German chartered flight
- German Official Leaks Report Denouncing Corona as ‘A Global False Alarm’
- City Leaders To Protesters: ‘Coming COVID-19 Second Wave Is Your Fault’
- Yale Epidemiologist: Hydroxychloroquine Should Be ‘Widely Available And Promoted Immediately’ As Standard Treatment
- “A W-Shaped Epidemic Is Now Emerging As Our Expected Case Forecast”
- Riots Breeding Ground for virus?
- Ukrainian Priests Tend to Sick in Biohazard Suits
- Experts warn of dire global health consequences if U.S. withdraws from the World Health Organization
- U.S. will terminate relationship with the World Health Organization in wake of Covid-19 pandemic
- CDC: 80,000 people died of flu last winter in U.S., highest death toll in 40 years
- CDC analysis suggests coronavirus likely started spreading in the U.S. in January
- New York City Is Expected To Enter First Phase of Reopening On June 8
- NO2 Levels Rebound in China – Pollution Seen From Space Clear Sign Major Lockdowns Over
- Evidence Shows Cloth Masks May Help Against COVID-19 – Especially Those With Several Layers of Cotton Cloth
- Connecticut’s coronavirus contact tracing plan plagued by issues
- Protesters increase the risk of getting, spreading coronavirus
- Now that I’m working from home, can I still claim overtime?
- Trump sets first campaign events after coronavirus shutdown
- ‘It was me. I know it was me.’ A nursing home aide, on passing the coronavirus to her mother, who later died
- Scientists warn apocalyptic bird flu that makes coronavirus look like a sniffle
- Scientists warn of ‘superspreaders’ as San Diego flocks to restaurants, salons
- Cash has become the new Typhoid Mary — no one wants to touch it in a pandemic
- In virus-hit South Korea, AI monitors lonely elders
- In the new downtown future, devoid of office workers, every day could be Sunday
- Survey shows benefits of pet ownership during pandemic
- After months of pessimism, nearly every major sport is preparing to come back
- Cats Can Spread COVID-19 Coronavirus Infection to Other Cats
- Study Confirms Cats Can Become Infected With COVID-19
- NYC coronavirus hot spots to get more tests, PPE ahead of reopening
- South Korea schools forced to close again after second wave of coronavirus
- Coronavirus began spreading in US as early as late January, CDC says
- Florida shows the right way to lock down for coronavirus — and loosen up
- NY state suspends liquor licenses over social distancing infractions
- Cuo show no mo’: Americans are officially over the Cuomo brothers
- Consumer spending plunges as Americans hoard cash amid coronavirus
- Judge says he can’t force Health Department to give nurses protective gear
- Hawaii governor to extend traveler quarantine past June
- Healthy people should wear masks only if caring for coronavirus patients, WHO says
- U.S. has sent two million doses of hydroxychloroquine to Brazil
- Can 8 million daily riders be lured back to N.Y. mass transit?
- Nicaragua has resisted imposing lockdown rules. Now the virus appears to be raging through the country.
- Hospital officials probing whether ventilators actually killed coronavirus patients
- South Africa has virus testing backlog of nearly 100,000
- Trump appeals to Africa with coronavirus aid as China increases efforts
Inside a coronavirus hospital in India, doctors see no end in sight
- Uber rolls out ride-by-hour option in some US cities
- States might turn to legalized gambling with budgets rocked by coronavirus
- Coronavirus hot spot Los Angeles can reopen restaurants, salons, Gov. Newsom says
- Trump cuts off WHO over China coronavirus ‘coverup’
- NY Gov. Cuomo must respond to Long Island strip club seeking to open amid coronavirus, judge says
- Mile-long line for food forms in one of the world’s wealthiest cities (Geneva)
- Fighter squadron taken off USS Gerald Ford after sailor tests positive for coronavirus
- Rage against the machine: Hundreds line up for jobless benefits at lone ATM
- People rent by-the-hour spaces to escape loved ones, homes during lockdown
- Anti-coronavirus lockdown protests are the Tea Party reborn
- Zappos offers a customer service line that people can call for anything — even to chat
- People are mistaking stimulus payments for junk or scam mail
B. Key Numbers & Trends
Note: Unless otherwise noted, all numbers in this Update are as of 5/31 and changes are since the prior day. Unless otherwise specified, all cases/deaths are confirmed cases/deaths that have been reported.
1. Cases & Tests
- Total Cases = 6,259,249 (+1.8%)
- New Cases (7 day average) = 109,256 (+1.6%) (+1,752)
- Total Cases = 1,837,170 (+1.1%)
- New Cases (7 day average) = 21,533 (+0.5%) (+106)
- Total Number of Tests = 17,672,567 (+395,597)
- Positive Test Rate (7 day average) = 5.3% (-0.4%)
- Note: 7 day average of new cases has increased slightly while testing is occurring in significant numbers, which is a positive trend. The decrease in the percentage of positive tests is also a positive trend.
- Worldwide Deaths
- Total Deaths = 373,697 (+0.9%)
- New Deaths (7 day average) = 3,895 (+1.4%) (+52)
- US Deaths
- Total Deaths = 106,195 (+0.6%)
- New Deaths (7 day average) = 985 (+0.3%) (+3)
- Note: Although the 7 day average increased slightly, the number of US deaths are trending down overall (the number of deaths on 5/31 was 638, a decrease of 37.1%)
- 5 Countries with Largest Number of Confirmed Deaths:
|Country||Total Deaths||New Deaths||Deaths Per 1M Pop|
- The number of new deaths in all 5 countries declined since the prior day, as did the number of new deaths on a worldwide basis (60% of the decline in new worldwide deaths came from these 5 countries).
- Deaths in these 5 countries = 62.9% of total worldwide deaths (-0.7%), and 28.3% of new worldwide deaths (-9.4%).
- US deaths = 28.4% of total worldwide deaths (-0.2%), and 20% of new worldwide deaths (-6.5%)
- States with Higher Per Capita Death Rate than National Average:
|State||Per Capita Deaths(per 1,000,000)||Increase in Per Capita Deaths||Compared to National Avg.|
|New York||1,538||+5||4.9x Nat’l Avg|
|New Jersey||1,318||+8||4.1x Nat’l Avg|
|Connecticut||1,106||+9||3.5x Nat’l Avg|
|Massachusetts||993||+11||3.1x Nat’l Avg|
|Rhode Island||678||+7||2.1x Nat’l Avg|
|Louisiana||600||+1||1.9x Nat’l Avg|
|Michigan||550||+3||1.7x Nat’l Avg|
|Pennsylvania||436||+3||1.4x Nat’l Avg|
|Illinois||425||+13||1.3x Nat’l Avg|
|Maryland||419||+4||1.3x Nat’l Avg|
|Delaware||376||+5||1.2x Nat’l Avg|
- All of these States are located in the Northeast other than MI and LA. All States are led by Democratic Governors other than LA and MD.
- The per capita deaths in NY, NJ, CT, MA and RI are at least 2x the national average, with NJ more than 4x and NY almost 5x the national average.
- The Death rate of all States (other than Louisiana) is accelerating faster than the national average, and the death rate of all of the States (other than Louisiana, Michigan and Pennsylvania) are growing more than 2x the national average, with the death rate of some States growing at 3x, 4x, 5x or 6x (or more) than the national average.
- Some of the highest growth in death rates are happening in States that remain under significant lockdown rules.
3. Countries/States To Watch
- Sweden is one of the few countries that did not impose a lockdown and has been cited by the WHO as a model for emerging from lockdowns
|Country||Total Deaths||New Deaths 7 Day Avg||Deaths Per 1M Pop|
- The 7 day average of new deaths for Sweden has declined slightly. However, it is too early to know if the number of new deaths have peaked (and will decrease further) or have merely paused before increasing further.
- Although per capita deaths in Sweden is less than Spain, UK, Italy and France (among other countries), Sweden’s per capita is much higher than its Nordic neighbors. And, Sweden’s per capita deaths have been increasing rapidly and is now significantly higher than the US.
- 5 States that Are Reopening Rapidly:
|State||Total Deaths||New Deaths 7 Day Avg||Deaths Per 1M Pop|
|GA||32||28 (+6)||193 (+4)|
|FL||2,452||31 (+0)||114 (+0)|
|TX||1,686||22 (+0)||58 (+0)|
|OH||2,110||27 (+0)||185 (+1)|
|OK||326||3 (+0)||84 (+0)|
|US||106,195||985 (+3)||321 (+2)|
- All of these States (other than OH) are in the south. All of these States are led by a Republican Governor and are rapidly reopening their economies (OK never imposed a lockdown).
- 7 day averages in new deaths in FL, TX, OH & OK are stable, which indicates that their reopenings are being managed effectively. For the last 10 days, the 7 day average for GA has been between 26 and 34 deaths, so the increase to 26 is well with the range and also appears stable, although more volatile than the other States.
- All 5 States have substantially lower deaths per 1 million of population than the national average, with TX, FLA and OK having less than half of the national average. Also, the rate of growth in per capita deaths in all of these States (other than GA) is less than half of the increase in the national average. The increase in per capita deaths in GA is double the national average, which is a warning sign of potential trouble.
C. By the Numbers
1. Assessing Your Risk: Fatality Rates and What Causes Them
- Based on what we currently know, there are 3 primary factors that affect fatality rates for C19: age, health condition and sex.
- But, based on recent data from NYC, one factor affects our risk far more than others: more than 99% of deaths have at least one underlying health condition. Almost 50% of deaths had 3+ co-morbidities. People with no health conditions account for less than 1% of deaths from C19. [Note: Statistics exclude cases for which the health condition of the person is unknown.]
- The CDC recently estimated that the average fatality rate for C19 is 0.26%, which is based on their estimate that 35% of infected persons are asymptomatic. [Note: Recent studies have indicated that the percentage of asymptomatic people may much higher, which would result in a much lower fatality rate.] The CDC estimate does not differentiate for age or underlying health conditions. As a result, the estimate overstates the risk to younger and healthier people.
- As discussed below, recent data from NYC breaks down death rates by age and health conditions, which can give us a more accurate way to assess risk. Based on the NYC data and estimates of health conditions per capita, the C19 death rate for people without any underlying health conditions is 0.019 per thousand whereas the date rate for people with underlying health conditions is 2.72 per thousand. [Note: see below for an explanation of how health conditions per capita were calculated.]
- In other words, the death rate among those with health conditions was 143 times more than the death rate among those with no heath conditions. While there are likely multiple factors contributing to the vast difference in death rates between those with and without underlying health conditions, it is clear that those without health conditions are substantially less likely to die than those with health conditions.
- Of those that died with underlying health conditions, 46% were 75+ years old, and approximately 95.8% of those that died with health conditions were 45+ years old.
- Bottom line: Based on current data, people with no underlying health conditions have little chance of dying from C19 (especially those under 44 years of age, with children having almost no risk of death). Although those with underlying health conditions have a significantly higher risk of dying than those with no health conditions, the chances of those with health conditions dying increase substantially with age (the death rate for those 75+ years old is 9.94 per thousand, which is 4.85 times those in the 45-64 age group)
Age & Health Conditions
- Although there are frequent reports in the news media of young people contracting serious cases of C19 and even dying, the disease in its serious form is overwhelmingly a disease of older people. Data on US deaths from the CDC in Figure 1 below portray this vividly.
Figure 1: US C19 Deaths (per million population) by Age
- It is also well known that those in poor health are more likely to die from C19. Data from New York City as of May 13 show that 11,370 C19 deaths (which is approx. 99% of all deaths for which the underlying health conditions were known) had additional underlying medical conditions (diabetes, lung disease, cancer, immunodeficiency, heart disease, hypertension, asthma, kidney disease, and GI/liver disease). By contrast, 65% of the US population as a whole reported “very good” or “excellent” health, according to CDC data.
- Moreover, the worse your health (number of underlying conditions prior to infection), the more likely you are to die.
- In a study of 528 patients who died in Italy early in the outbreak, virtually all of them had at least one co-morbidity (underlying non-C19 disease). Nearly half of the deaths had 3+ co-morbidities, as shown in Figure 2.
Figure 2: Italy C19 deaths (%) by number of co-morbidities
Is There Really an Age Effect?
- Old age and declining health go hand in hand. Could it be that the greater risk faced by those of advancing age is really just a reflection of their compromised health? Further examination of the New York City data suggests, at first glance, that this might be the case. Table 1 disaggregates NYC deaths (through May 13) by age and health.
Table 1: NYC deaths by age and underlying health condition
|Age||Number of Deaths||Share of deaths||With underlying conditions||W/o underlying conditions||Unknown if with underlying cond.|
|0 – 17 years old||9||0.06%||6||3||0|
|18 – 44 years old||601||3.9%||476||17||108|
|45 – 64 years old||3,413||22.4%||2,851||72||490|
|65 – 74 years old||3,788||24.9%||2,801||5||982|
|75+ years old||7,419||48.7%||5,236||2||2,181|
|TOTAL||15,230||100%||11,370 (74.6%)||99 (0.65%)||3,761 (24.75%)|
- Several points worth noting:
- At first glance, looking just at the “Share of deaths” column, the effect of age seems overwhelming – nearly half the deaths are in the 75+ category (only about 8% of the general population is this old).
- The number of deaths in the 75+ category are more than 10x the number of deaths in the 18 to 44 age group, more than 2x the number of deaths in the 45 to 64 age group, and almost 2x the number of deaths in the 65 to 74 age group.
- And the number of deaths in the 45 to 74 age groups is more than 12x the number of deaths in the 18 to 44 age group (the number of deaths in the 45+ age groups is more than 24x the number of deaths in the 18 to 44 age group). There are only 9 deaths in the 0 to 17 category (0.06%).
- Looking closer at the “Without underlying conditions” column, though, we see that healthy older people do not account for many deaths, including people 65+ years old. Only 7 people that were 65+ are known to have died with no underlying conditions, and only 2 people 75+ are known to have died with no underlying condition. Of note, the health condition was unknown for 3,761 people that died.
- Nearly all the deaths had some form of co-morbidity; people known to be healthy accounted for less than 1% of the deaths (as with the study in Italy).
- When we look at death rates (not share of deaths), though, and separate out the “with underlying conditions” population from the “without underlying conditions” population, we see there is an age effect in each, but much more so with those having underlying conditions. See Table 2 (with underlying health conditions) and Table 3 (without underlying health conditions).
Table 2: Death rate, by age, among those without underlying health conditions
|Age||Numbers of Deaths w/o Conditions||Population w/o health conditions (000)||Death rate(000)|
|0 – 17years old||3||1,633||0.002|
|18 – 44years old||17||2,501||0.007|
|45 – 64years old||72||958||0.075|
|65 – 74years old||5||111||0.045|
Table 3: Death rate, by age, among those with underlying health conditions
|Age||Numbers of Deaths with Conditions||Population with health conditions (000)||Death rate (000)|
|0 – 17years old||6||197||0.03|
|18 – 44years old||476||1,407||0.34|
|45 – 64years old||2,851||1,394||2.05|
|65 – 74years old||2,801||657||4.26|
- Among both healthy and unhealthy populations, death from C19 generally increases with age (although the death rate for healthy 75+ year olds was less than healthy people in the 45 to 75 year old groups). However, the death rate among those with underlying health conditions increases substantially with age (the rate of death for those 75+ years is more than 4.5x the rate for those 45 to 64 years old, and the rate of death for those 75+ was double the rate for those 65 to 74).
- Although the risk of dying with no underlying health conditions appears to be minimal, as noted above, more people without health conditions died in the 45 to 63 year old category than any other age group. We have not seen an explanation for why that age group would suffer more deaths than older age groups, but the number of older people in the data is quite small, so it may simply reflect that there were not many infected people in older age groups that had no underlying health conditions.
- Data for NYC population by age group is from Baruch College (see https://www.baruch.cuny.edu/nycdata/population-geography/age_distribution.htm), their source was US Census American Community Survey). Estimates for the population with health conditions are from the CDC for over 55 group (see https://www.cdc.gov/nchs/health_policy/adult_chronic_conditions.htm, and the Rand Corporation report Multiple Chronic Conditions in the United States (see http://www.fightchronicdisease.org/sites/default/files/TL221_final.pdf). Interpolation and averaging of sources were used where age groups did not match up exactly to the age groups in the NYC health data. Data on population groups without underlying health conditions is, naturally, the balance remaining after those with conditions are subtracted from the overall.
- This is a limited dataset for New York City at one period in time.
- The “Unknown” column tempers the definitiveness of the conclusion about health and age a little, though not much if we assume the unknowns are distributed like the knowns. [Note: we excluded the unknowns from our analysis as there is no way to know what the results would be, and absent evidence to the contrary it is reasonable to assume that unknowns would be distributed in approximately the same manner as the knowns.]
- These data reflect deaths, not C19 infections – many younger healthy people carry the virus without symptoms.
- These data from New York City show that both aging and being unhealthy, separately, contribute to a greater risk of dying from C19. The risk from being unhealthy, though, is far greater.
Fatality Rate by comorbidity:
|PRE-EXISTING CONDITION||DEATH RATE|
|Chronic respiratory disease||8.0%|
- Death Rate = (number of deaths / number of cases) = probability of dying if infected by the virus (%). This probability differs depending on pre-existing condition. The percentage shown below does NOT represent in any way the share of deaths by pre-existing condition. Rather, it represents, for a patient with a given pre-existing condition, the risk of dying if infected by C19. The percentages do not have to add up to 100%, as they do not represent share of deaths by condition.
B. Sex & Health Conditions
- Data provided by New York City Health as of April 14, for known sex of deceased:
|SEX||Deaths||Share of Deaths||With underlying conditions||Share within this category||Without underlying conditions||Share within this category||Unknown if with cond.||Share within this category|
- Men are dying at a significantly higher rate than woman, whether or not they have underlying conditions (men are dying at even higher rates than women (more than double) when no underlying conditions are present).
C. Risk of Death from C19 vs. Normal Annual Risk
[Note: While this is an interesting chart, we believe that it is comparing apples and oranges. In our view, the real issue is how much more is the risk of death due to C19, which would be added to the normal death rate.]
D. New Scientific Findings & Research
1. 10% of C19 patients with diabetes die within a week of hospitalization
- 10% of C19 patients with diabetes die within one week of being hospitalized, according to the first study of the virus to examine its impact on hospitalized patients.
- According to the research, published in Diabetologia, the journal of the European Association for the Study of Diabetes, 20% patients end up being intubated and needing a mechanical ventilator at that point, as well.
- The study analyzed 1,317 patients admitted to 53 public and private French hospitals between March 10 and 31.
- The findings also showed that 65% of C19 patients with diabetes admitted to the hospital are men, and the average age of all patients admitted who have diabetes is 70.
- The presence of diabetic complications and age increase the risk of death, and increased BMI, or one’s body mass index, is associated with both increased risk of needing mechanical ventilation and increased risk of death, the study found.
- “The risk factors for a severe form of C19 are identical to those found in the general population: age and BMI,” the researchers said in a statement.
2. The nose could be the body’s entry point to infection
- The nose is the probable starting point for C19 infections.
- Richard Boucher and Ralph Baric at the University of North Carolina at Chapel Hill and their colleagues tracked the ease with which the new coronavirus infects various cell types in the respiratory tract. The researchers found a gradient of infectivity that decreases from the upper to the lower respiratory tract: the most easily infected cells are in the nasal cavity, and the least easily infected deep in the lungs. (Y. J. Hou et al. Cell http://doi.org/dw2j; 2020). That gradient mapped neatly onto the distribution of cells that express ACE2, a protein that the coronavirus uses to enter cells.
- The authors speculate that the virus gets a foothold in the nose, then sneaks down the respiratory tract when breathed into the airways. They say the results support the use of masks and preventative measures such as nasal cleansing.
Note: The study can be found at:
3. New Study Outlines a Roadmap for Effective Treatment of C19
- In Frontiers in Immunology, a team of researchers from the U.S. Food and Drug Administration review all of the C19 clinical and research findings to date. They provide a breakdown of key immunological factors underlying the clinical stages of C19 illness that could potentially be targeted by existing therapeutic drugs.
- Dr. Montserrat Puig of the U.S. Food and Drug Administration, senior author of the review, stated that “there are multiple factors involved in determining if the patient’s immune response will be insufficient or successful in combating the infection. Our review is an overview of these factors and how they can be considered to define the context in which medications currently used for other diseases, or development of novel agents, can be utilized to prevent, ameliorate or cure C19.”
- We know that during the early stage of C19 people can show no symptoms or mild symptoms, and for many the disease resolves.
- For others it can be catastrophic. The illness can progress to a severe stage with manifestations including Acute Respiratory Distress Syndrome, accompanied by severe lung inflammation and damage. Patients with severe C19 are often admitted to intensive care units and require life support with medical ventilation.
- This review compiles and summarizes published up-to-date studies unraveling the factors leading to the cytokine storm and its consequences observed in C19, including the immunological events underlying the severe manifestation of the disease.
- The analysis is further supplemented with knowledge previously acquired from other coronaviruses including SARS-CoV and MERS-CoV.
- The authors underscore key immunological events that might tip the balance from a protective to a hyperinflammatory response leading to life-threatening conditions. They outline a promising list of currently available drugs that are either under study or under consideration for use in C19 based on their potential to influence these key immunological events.
- These drugs include those that could inhibit SARS-CoV-2 entry into host cells, antivirals with the potential to block SARS-CoV-2 replication or factors that could boost the antiviral response, monoclonal antibodies targeting pro-inflammatory cytokines that drive the hyperinflammatory response and therapeutics that could improve the function of the lungs.
- Puig states that “approaches to therapy in the early stage of the disease will differ from those in its severe late stage.” Adding that “as the results of clinical trials become available, it may become increasingly clear that there is likely no single magic bullet to resolve the disease but a combination of several interventions that target different key factors of C19 may well be required.”
- Puig cautions that “the research and data obtained from C19 studies are rapidly evolving and continuously updated. Thus, as clearly stated in our review, the information provided is a ‘lessons learned’ to date and describes the knowledge available at the time of the publication of the review.”
- The description of the immunological profile of the clinical stages of C19 provided in this review will enable more informed decisions about the type and timing of treatments to be evaluated in clinical trials.
- Puig explains that “our hope is that the information contained in our review will help professionals in C19 research develop new tools and agents to better treat those at high risk of severe C19.”
- The article can be found at: Lessons Learned to Date on COVID-19 Hyperinflammatory Syndrome: Considerations for Interventions to Mitigate SARS-CoV-2 Viral Infection and Detrimental Hyperinflammation
E. Potential Treatments
1. Blood plasma is our best drug
- A team of doctors and scientists are looking for C19 survivors whose plasma have virus-killing antibodies 10 to 50 times greater than other donors.
- Convalescent plasma therapy works by infusing ill patients with antibodies of people who survived C19. Researchers believe it may be one of the most effective therapies because it’s safe and has a proven track record with other infectious diseases. “Right now, our best drug is the one that’s manufactured by those patients and those individuals who have recovered from this disease,” says David Perlin, biomedical researcher and chief scientific officer at Hackensack Meridian Health Center for Discovery and Innovation.
- Perlin and his colleague, Dr. Michele Donato, the lead investigator for the study, got expedited approval from the FDA to collect and test donors’ plasma to find the people with high quantities of the most powerful antibodies. Fewer than one third of the thousands of survivors offering to donate qualify, “It looks like about 20% of people have really, really an extraordinarily good immune response,” says Dr. Donato. “And what we’re looking at is if giving a quantity of neutralizing antibodies is the best way to approach it. But that’s what this study will tell us.”
2. New Research Points to Treatment for C19 Cytokine Storms, Solution to Global Pandemic
- A transgenic mouse developed at Cincinnati Children’s to model the deadly childhood immune disease HLH (hemophagocytic lymphohistiocytosis) may play a key role in saving lives during the COVID-19 virus pandemic.
- One of the genetically engineered mouse strain’s inventors–Cincinnati Children’s cancer pathologist Gang Huang, PhD– is co-investigator on a small clinical trial that successfully tested a drug used to treat to HLH (ruxolitinib) to dramatically reverse respiratory and multi-system inflammation in severely ill C19 patients. Data from the Phase II clinical study is published in the Journal of Allergy and Clinical Immunology.
- The study involved 43 hospitalized patients diagnosed with severe C19 between February 9 and February 28 in Wuhan, China, believed to be ground zero for the pandemic. The multi-center study was led by Jianfeng Zhou, MD, PhD, Department of Hematology at Tongji Hospital, Tongji Medical College and Huazhong University of Science in Wuhan.
- Zhou is a longtime collaborator of Huang and colleagues at the Cincinnati Children’s HLH Center of Excellence, part of the Cancer and Blood Diseases Institute.
Ruxolitinib Shows Signs of Benefit
- Patients taking ruxolitinib were randomly selected to receive two daily 5mg oral doses of the anti-inflammatory drug, plus the standard of care treatment for C19. A randomly selected control group of 21 patients received a placebo along with the standard of care treatment.
- “Ruxolitinib recipients had a numerically faster clinical improvement,” study authors write in their report. “Significant chest CT improvement, a faster recovery from lymphopenia and favorable side-effect profile in ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.”
- Patients treated with ruxolitinib saw a shorter median time to clinical improvement compared to the control group. Researchers reported that 90% of ruxolitinib patients showed CT scan improvement within 14 days, compared with 61.9% of patients from the control group. Three patients in the control group eventually died of respiratory failure. All the severely ill patients who received ruxolitinib survived.
- More clinical testing of the drug is needed. A larger Phase III clinical trial RUXCOVID by Incyte and Novartis is now testing up to 400 severely ill C19 patients with the drug, according to Huang. Preliminary clinical data from the study is expected during the summer, he added.
- “This is the first therapy we know of that appears to work effectively to quiet the cytokine storm and inflammation in severe C19 disease, and there are no significant toxicities to patients who take the drug by two pills a day,” Huang said. “This is critical until we can develop and distribute enough effective vaccine to help prevent people from becoming infected.”
Calming the ‘Cytokine Storm’
- The so-called cytokine storm that inundates the bodies of severely ill C19 patients with inflammatory cells produced by the immune system is a common feature of children battling secondary HLH, which happens in patients where initial HLH treatment has not worked. Huang, who along with a large portion of the world’s scientific community was busy trying to study and find solutions to C19, noticed this common clinical feature of both illnesses.
- He also noticed that severe C19 disease clinical manifestations are very similar to those seen in transgenic laboratory mice created to faithfully mimic human secondary HLH in the lab. That preclinical laboratory research, some of it in collaboration with the researchers in Wuhan, China, helped identify the drug ruxolitinib for treating secondary HLH. The anti-inflammatory drug is also used to treat other blood diseases including leukemia.
- “I approached our research colleagues in Wuhan and explained our observations and recommended this drug be tested to quiet the cytokine storm in the multi-system inflammation in patients with severe C19 disease,” Huang said. “The disease was spreading very rapidly and many people were dying. We believed the existing clinical drug would help save lives. So, we worked to push it forward before there is an effective vaccine for everyone.”
- Huang said the work with colleagues in China was completed on a compressed timeframe as scientists around the world went on high alert to battle the pandemic in January. During their work, Huang and researchers in China found other clinical studies involving other diseases where ruxolitinib also had worked well at quieting inflammation, and testing on C19 patients proceeded.
- The full scientific article can be found at Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial
3. Can Alpha Blockers Ease Severe C19 Symptoms by Preventing ‘Cytokine Storm’
- For some C19 patients, the body’s immune response may be as destructive as the virus that causes the disease. The persistent high fevers, severe respiratory distress, and lung damage seen in some critically ill patients are all signs of an immune system in overdrive.
- Now, a new clinical trial will test a treatment that targets this overactive immune response, says Howard Hughes Medical Investigator Bert Vogelstein. He and his team at the Johns Hopkins University School of Medicine are currently recruiting individuals for the trial, which includes patients ages 45 to 85 at the Johns Hopkins Hospital who have C19 but who aren’t on a ventilator or in the ICU.
- Their treatment, a common type of prescription drug called an alpha blocker, might break a cycle of hyperinflammation before it ramps up, their findings from mouse studies and a recent analysis of medical claims data suggest.
- “The approach we’re advocating involves treating people who are at high risk early in the course of the disease, when you know they’re infected but before they have severe symptoms,” says Vogelstein. If the trial’s results suggest the drug is safe and effective against C19, it could potentially help many people recover safely at home and lessen the strain on hospital resources, he says.
- A hyperactive immune response isn’t unique to C19. People with autoimmune diseases and cancer patients receiving immunotherapy can experience similar symptoms. These responses are referred to as macrophage activation syndrome, cytokine release syndrome — or simply “cytokine storms.”
- When macrophages (and some other kinds of immune cells) detect virus particles, they send out alert messages by releasing various proteins known as cytokines. Those cytokines recruit other immune cells to the scene — an inflammatory response that, in moderation, helps the body fight off a virus. But macrophages can also release other signaling molecules, called catecholamines, that amplify this response further, triggering the release of more cytokines. The result is a runaway feedback loop, like a snowball getting bigger as it barrels down a hill.
- “It seems that once this process starts, there’s this inability to properly switch it off,” says Maximilian Konig, a rheumatologist at Hopkins who is helping to coordinate the trial.
- Before C19 hit, Vogelstein’s team was already exploring ways to ease the hyperinflammatory immune response in cancer patients treated with immunotherapy. The researchers were interested in drugs called alpha blockers, which are widely prescribed for prostate conditions and high blood pressure — and also interfere with the cell signaling that triggers cytokine storms. In theory, alpha blockers might stop a cytokine storm before it starts.
- Giving mice with bacterial infections an alpha blocker lessened cytokine storms and decreased deaths, Vogelstein’s team reported in the journal Nature in 2018. And, the researchers found, the treatment didn’t seem to harm other aspects of the immune response.
Staving off the storm
- As the C19 pandemic escalated in the United States over the past few months and severely ill patients presented with cytokine storm symptoms, the idea of testing alpha blockers in humans has become more urgent, Vogelstein’s team recently argued in the Journal of Clinical Investigation.
- To obtain approval for an alpha blocker clinical trial, Vogelstein’s team first surveyed medical claims data. They combed through records from people hospitalized for pneumonia and acute respiratory distress and analyzed whether patients’ outcomes were better if they had been taking alpha blockers for unrelated conditions. The team’s tentative conclusion: taking alpha blocker drugs correlated to a lower risk of death from respiratory distress.
- On its own, that’s not strong enough evidence to prescribe the drug for a wholly new disease like C19, says Susan Athey, an economist at Stanford University who collaborated with Vogelstein’s team on the claims analysis. But it helps bolster the case for the team’s clinical trial.
- In the trial, C19 patients will take gradually increasing doses of an alpha blocker called prazosin, sold under the brand name Minipress, over six days, says Chetan Bettegowda, a neurosurgeon at Hopkins who is helping to design and run the trials.
- Then, the team will evaluate whether people who received this treatment had a lower ICU admission rate or ventilator use than patients who received the standard treatment. They’ll follow each patient for 60 days, but preliminary data from the first patients could be available within weeks to months, Bettegowda says.
- If the trial’s results suggest alpha blockers are safe and effective, the team hopes to run a second trial with patients who have been diagnosed with C19 but are not yet hospitalized. They’re also encouraging colleagues at other hospitals to join their clinical trial efforts, to gather patient data more quickly.
- This treatment, if it works, would be a secondary form of prevention, Vogelstein says, mitigating symptoms before they become severe, rather than stopping infection in the first place. “Eventually, hopefully, a vaccine will be produced, and that will be the essence of prevention,” he says. “But until vaccines are available, secondary prevention makes a lot of sense.”
1. Novartis will start making coronavirus vaccine this month
- Swiss drugmaker Novartis will start producing a genetic coronavirus vaccine this month under a deal with Massachusetts researchers.
- AveXis, Novartis’ gene-therapy arm, agreed to manufacture the vaccine being developed by Massachusetts Eye and Ear and Massachusetts General Hospital. Production will start in time for clinical trials that are scheduled to begin in the second half of this year, according to a Thursday announcement.
- Researchers cast AveXis as a strong partner because it already has more than 1 million square feet of manufacturing capacity as the producer of the gene therapy Zolgensma, one of just two drugs of its kind available in the US.
- “We are uniquely poised to help the team move quickly toward this accelerated effort,” AveXis president Dave Lennon said in a statement.
- The agreement puts Novartis into the global race for a C19 vaccine that has already attracted pharmaceutical and biotech firms such as AstraZeneca, Moderna, Merck and Novavax. Clinical evaluations have started for 10 potential vaccines and more than 100 others are in pre-clinical stages, according to the World Health Organization.
- The Massachusetts vaccine uses a vector of an adeno-associated virus, or AAV — a kind of virus that does not cause disease — to deliver genetic code to produce “protein fragments” of the new coronavirus and trigger an immune response, according to researchers.
- The AveXis drug Zolgensma — which made headlines as the world’s most expensive drug with its $2.1 million price tag — also uses an AAV vector.
- “By partnering with an industry leader in AveXis that already produces AAV gene therapy products at large scales, we are more on track than ever to reaching our goal of developing a vaccine capable for wide distribution to prevent infection at population levels,” said Luk H. Vandenberghe, director of Massachusetts Eye and Ear’s Grousbeck Gene Therapy Center.
2. Big gene therapy names line up behind experimental C19 vaccine
- An early stage vaccine against C19 based on the same basic technology used in gene therapy is gaining some support from some of that field’s biggest names.
- Earlier this year, James Wilson, a gene therapy pioneer, got a call from Luk Vandenberghe, who had been a graduate student in Wilson’s lab two decades ago. Vandenberghe wondered if a virus they had worked on as a potential component of gene therapies might work as part of a vaccine against the coronavirus.
- “It’s a great idea,” said Wilson, who heads the Gene Therapy Program at the University of Pennsylvania. “What can I do to help?”
- Vandenberghe, director of the Grousbeck Gene Therapy Center at Massachusetts Eye and Ear, is taking Wilson up on his offer. On Thursday, the Grousbeck center announced a collaboration with Penn to conduct necessary animal tests of the new gene therapy, called AAVCOVID. At the same time, AveXis, the gene therapy unit of the drug giant Novartis, has signed up to manufacture supplies of the experimental vaccine for human clinical trials at no cost. The studies are expected to begin in the second half of this year.
- There is a desperate need for speed, and to develop every potential vaccine candidate, Vandenberghe said, because it is uncertain what will work.
- “Every dose of a somewhat efficacious vaccine will be consumed,” Vandenberghe said. “This is not ‘first to market.’ This is all hands on deck.”
- David Lennon, the president of the AveXis unit, said that Novartis did not want the process of hammering out a deal to slow down Vandenberghe clinical studies.
- “At this point, given the early nature of the technology, as well as the speed at which we wanted to move and the fact that this is a public health emergency, we didn’t want to spend time worrying about exactly where the commercial aspects of this partnership land,” Lennon said.
- Three contract manufacturing players, Viralgen, Aldevron, and Catalent, have also signed on to help with manufacturing.
- The reason all these companies — and Wilson — can sign on to make this vaccine is that it uses the same type of virus, known as an adeno-associated virus, that is the backbone of most gene therapies. Gene therapy tries to replace missing or damaged genes by using a virus to sneak the genetic material into cells, which is, basically, what viruses do. Some vaccine technologies, including those being developed for C19, try to take a similar approach.
- One big difference: the amount of AAV in a vaccine would be 1,000 to 10,000 times smaller than in gene therapies such as Novartis’ Zolgensma, which treats a rare and lethal disease called spinal muscular atrophy in infants.
- Gene therapy researchers turned to adeno-associated virus in the 2000s after a disaster. A patient in a study run by Wilson employing a gene therapy that used adenovirus, which causes flu-like symptoms, had an immune response that led to organ failure and death. As a result, the entire field, which had seen on the cusp of developing treatments, was effectively frozen.
- Unlike adenovirus, adeno-associated virus, or AAV, is very good at evading the immune system, which means that it doesn’t provoke that kind of response. But the virus Vandenberghe developed while working with Wilson, which was derived from AAVs found in monkeys, did provoke the immune system somewhat.
- While that meant this particular type of AAV was not suited to gene therapy, provoking the immune system is exactly what researchers want a vaccine to do. In fact, several other C19 vaccines use an adenovirus to deliver a genetic payload that then provokes an immune response.
- The adenovirus was a necessity for developing, for instance, experimental HIV vaccines, Vandenberghe said. But he thinks AAV may have advantages when it comes to C19, including safety. Another advantage is easy to understand: all the manufacturing capacity for growing AAV that companies like Novartis have built in order to be able to manufacture gene therapy products.
- “Yes, we are six months or so delayed compared to some of the first movers,” Vandenberghe said, “but in the end we will need something that is highly safe, highly potent, and highly scalable. And we believe we check boxes in each of these three categories.”
- Now he has to conduct the studies to find out whether or not he is right.
1. It’s Not Whether You’re Exposed to the Virus, But How Much
- When experts recommend wearing masks, staying at least six feet away from others, washing your hands frequently and avoiding crowded spaces, what they’re really saying is: Try to minimize the amount of virus you encounter.
- A few viral particles cannot make you sick — the immune system would vanquish the intruders before they could. But how much virus is needed for an infection to take root? What is the minimum effective dose?
- A precise answer is impossible, because it’s difficult to capture the moment of infection. Scientists are studying ferrets, hamsters and mice for clues but, of course, it wouldn’t be ethical for scientists to expose people to different doses of the coronavirus, as they do with milder cold viruses.
- “The truth is, we really just don’t know,” said Angela Rasmussen, a virologist at Columbia University in New York. “I don’t think we can make anything better than an educated guess.”
- Common respiratory viruses, like influenza and other coronaviruses, should offer some insight. But researchers have found little consistency.
- For SARS, also a coronavirus, the estimated infective dose is just a few hundred particles. For MERS, the infective dose is much higher, on the order of thousands of particles.
- The coronavirus is more similar to the SARS virus and, therefore, the infectious dose may only be hundreds of particles, Dr. Rasmussen said.
- But the virus has a habit of defying predictions.
- Generally, people who harbor high levels of pathogens — whether from influenza, H.I.V. or SARS — tend to have more severe symptoms and are more likely to pass on the pathogens to others.
- But in the case of the coronavirus, people who have no symptoms seem to have viral loads — that is, the amount of virus in their bodies — just as high as those who are seriously ill, according to some studies.
- And coronavirus patients are most infectious two to three days before symptoms begin, less so after the illness really hits.
- Some people are generous transmitters of the coronavirus; others are stingy. So-called super-spreaders seem to be particularly gifted in transmitting it, although it’s unclear whether that’s because of their biology or their behavior. [Note: A recent study indicated that 80% of the infections may be caused by 10% of those who are infected.]
- On the receiving end, the shape of a person’s nostrils and the amount of nose hair and mucus present — as well as the distribution of certain cellular receptors in the airway that the virus needs to latch on to — can all influence how much virus it takes to become infected.
- A higher dose is clearly worse, though, and that may explain why some young health care workers have fallen victim even though the virus usually targets older people.
- The crucial dose may also vary depending on whether it’s ingested or inhaled.
- People may take in virus by touching a contaminated surface and then putting their hands on their nose or mouth. But “this isn’t thought to be the main way the virus spreads,” according to the CDC. That form of transmission may require millions more copies of the virus to cause an infection, compared to inhalation.
- Coughing, sneezing, singing, talking and even heavy breathing can result in the expulsion of thousands of large and small respiratory droplets carrying the virus.
- “It’s clear that one doesn’t have to be sick and coughing and sneezing for transmission to occur,” said Dr. Dan Barouch, a viral immunologist at Beth Israel Deaconess Medical Center in Boston.
- Larger droplets are heavy and float down quickly — unless there’s a breeze or an air-conditioning blast — and can’t penetrate surgical masks. But droplets less than 5 microns in diameter, called aerosols, can linger in the air for hours.
- “They travel further, last longer and have the potential of more spread than the large droplets,” Dr. Barouch said.
- Three factors seem to be particularly important for aerosol transmission: proximity to the infected person, air flow and timing.
- A windowless public bathroom with high foot traffic is riskier than a bathroom with a window, or a bathroom that’s rarely used. A short outdoor conversation with a masked neighbor is much safer than either of those scenarios.
- Recently, Dutch researchers used a special spray nozzle to simulate the expulsion of saliva droplets and then tracked their movement. The scientists found that just cracking open a door or a window can banish aerosols.
- “Even the smallest breeze will do something,” said Daniel Bonn, a physicist at the University of Amsterdam who led the study.
- Observations from two hospitals in Wuhan, China, published in April in the journal Nature, determined much the same thing: more aerosolized particles were found in unventilated toilet areas than in airier patient rooms or crowded public areas.
- This makes intuitive sense, experts said. But they noted that aerosols, because they are smaller than 5 microns, would also contain much less, perhaps millions-fold less, virus than droplets of 500 microns.
- “It really takes a lot of these single-digit size droplets to change the risk for you,” said Dr. Joshua Rabinowitz, a quantitative biologist at Princeton University.
- Apart from avoiding crowded indoor spaces, the most effective thing people can do is wear masks, all of the experts said. Even if masks don’t fully shield you from droplets loaded with virus, they can cut down the amount you receive, and perhaps bring it below the infectious dose.
- “This is not a virus for which hand washing seems like it will be enough,” Dr. Rabinowitz said. “We have to limit crowds, we have to wear masks.”
2. Yikes! Saliva Droplets From Mild Cough Travel Up to 18 Feet
- Saliva droplets can travel large distances, depending on environmental conditions such as wind speed, temperature, pressure and humidity. Wind shown blowing left to right at speeds of 4 kph (top) and 15 kph (bottom) can transport saliva droplets up to 6 meters (18 feet).
- Current social distancing guidelines of 6 feet may be insufficient, because a mild cough occurring in low wind speeds of 4-15 kph can propel saliva droplets 18 feet.
- Airborne transmission of viruses, like the virus causing C19, is not well understood, but a good baseline for study is a deeper understanding of how particles travel through the air when people cough.
- In a paper published in Physics of Fluids, from AIP Publishing, Talib Dbouk and Dimitris Drikakis discovered that with even a slight breeze of 4 kph, saliva travels 18 feet in 5 seconds.
- “The droplet cloud will affect both adults and children of different heights,” Drikakis said. “Shorter adults and children could be at higher risk if they are located within the trajectory of the traveling saliva droplets.”
- Saliva is a complex fluid, and it travels suspended in a bulk of surrounding air released by a cough. Many factors affect how saliva droplets travel, including the size and number of droplets, how they interact with one another and the surrounding air as they disperse and evaporate, how heat and mass are transferred, and the humidity and temperature of the surrounding air.
- To study how saliva moves through air, Dbouk and Drikakis created a computational fluid dynamics simulation that examines the state of every saliva droplet moving through the air in front of a coughing person. Their simulation considered the effects of humidity, dispersion force, interactions of molecules of saliva and air, and how the droplets change from liquid to vapor and evaporate.
- The computational domain in the simulation is a grid representing the space in front of a coughing person. The analysis involved running partial differential equations on 1,008 saliva droplets and solving approximately 3.7 million equations in total.
- “Each cell holds information about variables like pressure, fluid velocity, temperature, droplet mass, droplet position, etc.,” Dbouk said. “The purpose of the mathematical modeling and simulation is to take into account all the real coupling or interaction mechanisms that may take place between the main bulk fluid flow and the saliva droplets, and between the saliva droplets themselves.”
- Further studies are needed to determine the effect of ground surface temperature on the behavior of saliva in air and to examine indoor environments, where air conditioning significantly affects the particle movement through air.
- “This work is vital, because it concerns health and safety distance guidelines, advances the understanding of spreading and transmission of airborne diseases, and helps form precautionary measures based on scientific results,” said Drikakis.
1. Immunity to Coronaviruses: Here’s What We Know So Far
- A new review discusses the findings from over 40 studies on coronavirus immunity and what they could mean for the Covid-19 pandemic.
- Written by top UK virologists, the article discusses the existing knowledge about immune responses to the SARS-CoV-2 and other coronaviruses, and how this could be used to inform virus control strategies. The review, which is free to read in the Journal of General Virology (JGV), collates the available scientific evidence in a number of key areas, including how long immunity to coronaviruses lasts and the prospect of antibody testing.
[Note: the article can be found at The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection]
- In the review, Professors Paul Kellam and Wendy Barclay from Imperial College London examine what is so far known about immunity to coronaviruses including SARS, MERS and the four strains of seasonal coronaviruses that circulate in humans every winter. The article goes on to suggest that SARS-CoV-2 could become the fifth seasonal coronavirus with epidemics of the virus occurring over the next several years.
- “SARS-CoV-2 is a new virus in humans and because of this we are having to learn quickly many of its basic properties. In the absence of such data right now, we can try to make predictions about the immune response to SARS-CoV-2 by re-examining what we know about the two epidemic coronavirus of humans, SARS and MERS and the four seasonal human coronavirus. We need to be cautious about inferring too much, but it is a good place to start.’
- “We do not really know what happens on the pathway of a new coronavirus in humans becoming an endemic seasonal infection, but it could be that when the four seasonal coronavirus first jumped from animals into humans they were much like SARS-CoV-2 in their transmission and pathogenesis.
- Over time as population immunity to the seasonal coronavirus became widespread, the amount of severe disease probably declined. However, seasonal coronavirus can still cause pneumonia in some people,” said Professor Kellam.
- A number of factors, including severity of disease influence how long antibody protection against both SARS and MERS lasts. Studies have shown that antibody protection wanes over time.
- For seasonal coronaviruses where disease is mild, there have even been reports of reinfection after as little as 80 days.
- “We need to find out many things about SARS-CoV-2 immunity, such as how good the immune response is and how long it lasts. We also need to understand if people with mild or asymptomatic infections develop a strong or weak immune response and what measurable properties of immunity predict protection from infection. When we know more about these things, we will be better able to understand how SARS-CoV-2 infections will continue over time.
- However, vaccines are not infections, therefore it is likely that some of the vaccines candidates will be better at inducing long lasting immunity and protection from infection,” said Professor Kellam.
- The authors also discuss the currently available antibody tests for SARS-CoV-2 and explain the differences between these tests, their accuracy and limitations. Knowing the level of immunity to SARS-CoV-2 in the population could be key in controlling the spread of disease and understanding how many people are at risk of infection.
- “Understanding immune responses to these viruses is on many people’s minds- from the public hearing about vaccines, testing and antibodies, to policy makers, and scientists working on or with an interest in the current pandemic.” said Alain Kohl, Deputy Editor-in-Chief of JGV). The Editor-in-Chief Paul Duprex added: “This review gives an up to date, and superbly researched overview of this field. Many people will find areas or topics of interest in this article, that should help them understand the important discussions going on. We are delighted to see it published in the journal.”
2. Monkeys develop immunity to coronavirus. Can humans?
- A small study published Wednesday in the journal Science offers promising evidence to suggest that recovery from C19 could lead to immunity against reinfection.
- The study, from researchers at Beth Israel Deaconess Medical Center in Boston, involved nine rhesus macaques — monkeys that share a majority of their genes with humans. The macaques were infected with the coronavirus and later recovered — and more than one month later, they were re-exposed to the virus.
- All of the macaques had developed antibodies against the virus, the researchers found, and had “near-complete protection” against the virus when they were re-exposed — a sign that they had developed immunity.
- Still, more research is needed to determine whether the findings also apply to humans, as well as to determine how long this immunity may last.
[Note: The World Heath Organization has stated that there is not yet any proof that infection provides immunity. While that is true, we tend to agree with the chief epidemiologist of Sweden, who said that we can infer that infection provides immunity because there are no known cases of anyone being reinfected, which would be highly unlikely if people could be reinfected. However, it is still uncertain how long immunity lasts.]
I. Concerns & Unknowns
1. C19 can cause debilitating long-term illness
- In the fall of 2009, one of us, Beth, was hit by an illness she suspects was H1N1 flu, which was circulating then. In 2012, the other, Brian, developed a sudden fever, which his doctors said was also likely of viral origin.
- Neither of us recovered, and we’re both disabled to this day.
- I was once a hard-working person. Now, I’m disabled with a mysterious illness.
- The long-term illnesses that can follow viral infections can be devastating — and are devastatingly common. In 2015, the nation’s top medical advisory body, the Institute of Medicine, estimated that between 800,000 and 2.5 million U.S. residents live with the illness or illnesses awkwardly named myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). An estimated three-quarters of these cases were triggered by viral or bacterial infections.
- Now, as a new pandemic virus is burning through the world and causing many deaths, researchers are raising alarms that the coronavirus and the disease it causes will also leave in its wake a potentially large population with post-viral problems that could be lifelong and, in some cases, disabling.
- At the NIH and elsewhere, scientists who have been studying post-viral ME/CFS are seizing the opportunity to focus on C19 patients. They want to understand what biological factors separate those who regain their health from those who remain sick.
- “We want to look at who recovers and who doesn’t,” said Avindra Nath, the head of clinical neurology at NIH’s Clinical Center in Bethesda, Md., who is gearing up to study C19 patients. “It’s quite possible some will never get their health back.”
- In addition to emerging reports of damage to lungs, kidneys and hearts, C19 patients are complaining of ongoing crushing fatigue, muscle pain, cognitive problems and other symptoms that anyone with ME/CFS is very familiar with.
- “I’m 69 days after my first symptoms and still feeling fatigued,” wrote Canadian comedian Wayne Jones on Twitter, saying he has tested positive for the new coronavirus. “I also have sore eyes, and weakness and headaches that come and go. All signs point to post-viral fatigue.”
- Sometimes a precursor to ME/CFS post-viral fatigue syndrome can occur after virtually any viral infection. Symptoms wax and wane; a person can feel fine one day and terrible the next. Exercise or other usual activities can bring fever and often symptoms rushing back. Although there is no known treatment, these problems often resolve on their own.
- But patients who have experienced post-viral fatigue syndrome advise the newly ill to rest, rest and rest some more, as returning to normal activities can trigger relapses. If symptoms continue for 6 months or longer, post-viral fatigue syndrome can convert to a diagnosis of ME/CFS, which is usually lifelong and often devastating. Up to 25% of ME/CFS patients are housebound or bedbound for years. There are no treatments approved by the Food and Drug Administration.
- A survey organized by a group of C19 patients called the Body Politic shows that many coronavirus symptoms overlap with those of post-viral fatigue syndrome. Fatigue, including severe fatigue, brain fog — problems with concentration and thinking — chills and sweats, and sleep problems were commonly reported among 640 respondents, who were recruited from online support groups. The Body Politic, which includes some patients with expertise in survey design and statistics, calculated that respondents had just a 20% chance of being symptom-free 50 days after the illness began. The group cautioned that while the survey suggests many respondents had long illnesses, the results may not apply to the broader population of C19 patients.
- The coronavirus is too new to say whether such lingering symptoms represent an extended C19 illness or a post-viral syndrome. But researchers suspect at least some covid patients will remain sick and eventually develop post-viral ME/CFS. Their suspicions are grounded in previous research. Studies on other outbreaks — including those of Epstein-Barr virus, Ross River fever and Q fever — have shown that up to 12% of people who fell acutely ill never regained full health. Many were eventually diagnosed with ME/CFS.
- After the first SARS epidemic, which sickened 8,000 people worldwide in 2002-2003, one study found that 27 percent of 369 survivors of that variety of coronavirus met the criteria for chronic fatigue syndrome several years later. If figures like this are seen with this novel coronavirus, SARS-CoV-2, which epidemiologists warn will eventually infect 50 to 70% of all U.S. residents, our nation is on track for a devastating wave of millions of patients with chronic post-viral illnesses.
- “The most important study of several we’re starting is to get coronavirus-infected patients and follow them over time to see if they convert to ME/CFS,” said Ron Davis, a geneticist at Stanford University. His adult son, Whitney Dafoe, is seriously ill with the disease.
- “If you point out the fact that you might not ever get over C19, it’ll put people’s attention on this problem,” Davis said. “We need doctors to be reading C19 information and be on the lookout for people who never get well. I think that’s extremely important.”
2. Many remain afraid to go to a hospital over C19 fears
- A new survey reinforces the fact that many Americans’ fears of contracting C19 at a hospital are keeping them from seeking essential care.
- The new survey, conducted by the Society for Cardiovascular Angiography & Intervention, included responses from around 1,000 U.S. adults over the age of 30.
- It found that 36% of respondents view going to the hospital as risky behavior, which is higher than the number who view going to a salon as risky (27%) and those who would reconsider going to the beach (16%).
- Asked further about going to a hospital, 61% said they felt they were somewhat or very likely to acquire C19 there.
- Half of respondents said they were more afraid of contracting the infection than they were of experiencing a heart attack or stroke, while nearly 60% said the same about a family member.
I. The Road Back?
1. We’re Reopening Notre Dame – It’s Worth the Risk
By Father John I. Jenkins, President of the University of Notre Dame
- Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, is a distinguished immunologist and an advocate for public health. I have the privilege of sharing with him an education in Catholic schools laden with the study of classical texts, philosophy and theology.
- Dr. Fauci credits such an education with giving him his impressive ability to explain complex medical facts to general audiences and present cogent arguments.
- He consistently says that he speaks as a scientist, offering us the best scientific information available to guide our response to the coronavirus pandemic. His advice is invaluable. There are, however, questions that a scientist, speaking strictly as a scientist, cannot answer for us.
- For questions about moral value — how we ought to decide and act — science can inform our deliberations, but it cannot provide the answer.
- At the University of Notre Dame, we recently announced our plans to return students to campus for the fall semester. In order to reduce the chances that students from around the country and the world with multiple departures and returns will carry pathogens with them, we will bring students back two weeks early, forgo a fall break and finish the semester before Thanksgiving.
- As soon as students arrive in August, we will conduct orientations to welcome them back in the Covid-19 era. We will also institute extensive protocols for testing; contact tracing and quarantining; and preventive measures, such as hand-washing, physical distancing and, in certain settings, the wearing of masks. This is how we can restore in-person classes safely.
- Athletic competition presents another set of challenges. We believe we can, with aggressive testing, hygiene and careful monitoring, keep student-athletes safe. Indeed, keeping healthy relatively small cadres of student-athletes, coaches and support staff members is a less daunting challenge than keeping safe the several thousand other people in the campus community.
- Fans in the stadium, however, are a different matter. Fighting Irish fans regularly fill Notre Dame Stadium’s 80,000 seats. I see no way currently to allow spectators unless we restrict admissions so that physical distancing is possible.
- Our focus to this point has been on restarting our educational and research efforts, and we will soon turn to answer the question of how many games we will play, when we will play them and how many fans will be in the stadium.
- With these and other steps — informed by the best medical advice we can find — we believe we can keep our campus environment healthy.
- Our decision to return to on-campus classes for the fall semester was guided by three principles that arise from our core university goals. First, we strive to protect the health of our students, faculty, staff and their loved ones. Second, we endeavor to offer an education of the whole person — body, mind and spirit — and we believe that residential life and personal interactions with faculty members and among students are critical to such an education. Finally, we seek to advance human understanding through research, scholarship and creative expression.
- If we gave the first principle absolute priority, our decision about reopening would be easy. We would keep everyone away until an effective vaccine was universally available.
- However, were we to take that course, we would risk failing to provide the next generation of leaders the education they need and to do the research and scholarship so valuable to our society. How ought these competing risks be weighed? No science, simply as science, can answer that question. It is a moral question in which principles to which we are committed are in tension.
- We all hope for an effective vaccine that will put Covid-19 behind us. Yet we cannot and should not assume that a vaccine will be available soon, nor, indeed, that another pandemic will not follow close behind. We live in a global society, and it is possible that animal-to-person contact in an open market somewhere may again cause a pandemic disrupting our society.
- We may need to reconcile ourselves to the fact that we are facing not simply a passing crisis, but a new normal. For that and similar challenges, we need moral insight.
- We are in our society regularly willing to take on ourselves or impose on others risks — even lethal risks — for the good of society. We send off young men and women to war to defend the security of our nation knowing that many will not return. We applaud medical professionals who risk their health to provide care to the sick and suffering. We each accept the risk of a fatal traffic accident when we get in our car.
- The pivotal question for us individually and as a society is not whether we should take risks, but what risks are acceptable and why. Disagreements among us on that question are deep and vigorous, but I’d hope for wide agreement that the education of young people — the future leaders of our society — is worth risking a good deal.
- Indeed, the mark of a healthy society is its willingness to bear burdens and take risks for the education and well-being of its young. Also worthy of risk is the research that can enable us to deal with the challenges we do and will face.
- We have availed ourselves of the best medical advice and scientific information available and are assiduously planning a reopening that will make the campus community as safe as possible. We believe the good of educating students and continuing vital research is very much worth the remaining risk.
- In our classical, humanistic educations, both Dr. Fauci and I came across the texts of Aristotle, who defined courage not as simple fearlessness, but as the mean between a rashness that is heedless of danger and a timidity that is paralyzed by it. To possess the virtue of courage is to be able to choose the proper mean between these extremes — to know what risks are worth taking, and why.
- Perhaps what we most need now, alongside science, is that kind of courage and the practical wisdom it requires. Notre Dame’s recent announcement about reopening is the attempt to find the courageous mean as we face the threat of the virus and seek to continue our mission of education and inquiry.
J. Practical Information & Other Useful Information
1. Flying during a Pandemic – What’s It Like and How To Reduce Risk
- One of our editors from Atlanta, Brian Sivy, has been reporting on experiences during the Pandemic. He recently flew on a Delta flight to Florida. If you’re wondering what it’s like to fly during C19 and if it’s safe, here is his story.
- In 2019, nearly 110 million travelers passed through the Atlanta Airport making it the world’s busiest airport. On a daily basis, that’s more than 300,000 passengers a day.
- On April 30, the number of passengers that went through security checkpoints was down to 3,500 people, instead of the typical 70,000, and a total of 10,000 travelers passed through the terminal, including connecting passengers.
- In the new pandemic world, the airport is like a ghost-town. Instead of driving around looking for a parking spot, an endless number of prime parking spots are available. The Departure area is also largely empty of passengers.
- Depending on your security clearance (TSA-precheck or CLEAR), wait times can be minimal due to the shorter lines. Nonetheless, don’t assume you’ll breeze through the lines. Airlines have staffed check-ins and baggage check areas with minimal staff. I noted a very long line of passengers waiting to check their bags.
- Airlines have cut the number of flights significantly and planes are starting to fill up. The middle seats are open, but on my outbound and inbound flights, I would estimate both flights were between 50-66% full. In the era of social distancing, this may make you feel very uncomfortable.
- You will experience moments that are uncomfortable. For example, a Delta flight attendant stood next to a seated flight attendant and proceeded to have a lengthy conversation. The seated Delta flight attendant had lowered his mask and was talking very loudly. By my estimate, this violated at least 3 CDC recommendations: (1) not maintaining a safe distance, (2) talking too loudly, and (3) not wearing a face mask.
- There are a number of best practices you can take to minimize your exposure to C19. Here are my safety tips:
- Consider checking your bag (but be aware you may have to wait in a longer line to check your bag). Passing through security will require you to touch the security bins and to touch the overhead bins
- I highly recommend having TSA-precheck clearance at a minimum and a CLEAR membership to minimize the amount of extra steps required to clear through security. Without these clearances, you’ll have to remove computers, gels, liquids and solids and place them in a security bin. That may triple or quadruple the number of touches.
- Wear a secure mask, preferably, an N95 or KN95 mask
- Have hand sanitizer on hand and use it frequently. For example, after you place your bags in the security or overhead bins
- Bathrooms are extremely high-risk areas. Choose your bathroom breaks wisely. Airport vs on-board plane. A flushed toilet represents one of the greatest areas of aerosol transmission risks. Wash your hands!
- Carry Clorox wipes (or similar wipe). I took a roll out of a Clorox tube and put it in a ziploc bag. Use it to wipe down your bag, your tray table, seat belt and head/arm rests. Airlines say they are sanitizing planes between flights but an extra layer of caution is worth the piece of mind.
- Wash your hands often, and stop touching your face (the mask will help)
- Choose a window seat and avoid areas close to the bathrooms. You’ll minimize your exposure to passengers walking down the aisle or using the bathroom
- Delta and many other airlines are boarding the back of the plane first. You should wait until the last possible minute to board your plane. Why add any extra time to your being on the plane?
- Delta is passing out pre-packaged snacks (water and crackers). If you’re on a relatively short flight, consider passing up all service. That’s one less thing you have to touch
- So, is it safe? There are certainly risks associated with flying. With planes approaching more than 50% full, the risks are only greater that someone on the plane may have C19
- You can minimize your risk of exposure by being careful, limiting your touching of surfaces, and washing/sanitizing your hands often, and wearing a mask (preferably an N95 or a KN95 mask)