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Archive for the ‘Economic Impact of Coronavirus Pandemic’ Category

The Inequality and Health Disparity seen with the COVID-19 Pandemic Is Similar to Past Pandemics

Curator: Stephen J. Williams, PhD

2019-nCoV-CDC-23311

It has become very evident, at least in during this pandemic within the United States, that African Americans and poorer communities have been disproportionately affected by the SARS-CoV2 outbreak . However, there are many other diseases such as diabetes, heart disease, and cancer in which these specific health disparities are evident as well :

Diversity and Health Disparity Issues Need to be Addressed for GWAS and Precision Medicine Studies

Personalized Medicine, Omics, and Health Disparities in Cancer:  Can Personalized Medicine Help Reduce the Disparity Problem?

Disease like cancer have been shown to have wide disparities based on socioeconomic status, with higher incidence rates seen in poorer and less educated sub-populations, not just here but underdeveloped countries as well (see Opinion Articles from the Lancet: COVID-19 and Cancer Care in China and Africa) and graphics below)

 

 

 

 

 

 

 

 

 

 

In an article in Science by Lizzie Wade, these disparities separated on socioeconomic status, have occurred in many other pandemics throughout history, and is not unique to the current COVID19 outbreak.  The article, entitled “An Unequal Blow”, reveal how

in past pandemics, people on the margins suffered the most.

Source: https://science.sciencemag.org/content/368/6492/700.summary

Health Disparities during the Black Death Bubonic Plague Pandemic in the 14th Century (1347-1351)

During the mid 14th century, all of Europe was affected by a plague induced by the bacterium Yersinia pestis, and killed anywhere between 30 – 60% of the European population.  According to reports by the time the Black Death had reached London by January 1349 there had already been horrendous reports coming out of Florence Italy where the deadly disease ravished the population there in the summer of 1348 (more than half of the city’s population died). And by mid 1349 the Black Death had killed more than half of Londoners.  It appeared that no one was safe from the deadly pandemic, affecting the rich, the poor, the young, the old.

However, after careful and meticulous archaeological and historical analysis in England and other sites, revealed a distinct social and economic inequalities that predominated and most likely guided the pandemics course throughout Europe.   According to Dr. Gwen Robbins Schug, a bio-archaeologist at Appalachian State University,

Bio-archaeology and other social sciences have repeatedly demonstrated that these kinds of crises play out along the preexisting fault lines of each society.  The people at greatest risk were often those already marginalized- the poor and minorities who faced discrimination in ways that damaged their health or limited their access to medical care even in pandemic times.

At the start of the Black Death, Europe had already gone under a climactic change with erratic weather.  As a result, a Great Famine struck Europe between 1315-17.  Wages fell and more people fell into poverty while the wealthiest expanded their riches, leading to an increased gap in wealth and social disparity.  In fact according to recordkeeping most of Englanders were living below the poverty line.

Author Lizzie Wade also interviewed Dr. Sharon, DeWitte, a biological anthropologist at University of South Carolina, who looks at skeletal remains of Black Death victims to get evidence on their health status, like evidence of malnutrition, osteoporosis, etc.   And it appears that most of the victims may have had preexisting health conditions indicative of poorer status.  And other evidence show that wealthy landowners had a lower mortality rate than poorer inner city dwellers.

1918 Spanish Flu

Socioeconomic and demographic studies have shown that both Native American Indians and African Americans on the lower end of the socioeconomic status were disproportionately affected by the 1918 Spanish flu pandemic.  According to census records, the poorest had a 50% higher mortality rate than wealthy areas in the city of Oslo.  In the US, minors and factory workers died at the highest rates.  In the US African Americans had already had bouts with preexisting issues like tuberculosis and may have contributed to the higher mortality.  In addition Jim Crow laws in the South, responsible for widespread discrimination, also impacted the ability of African Americans to seek proper medical care.

From the Atlantic

Source: https://www.theatlantic.com/politics/archive/2016/05/americas-health-segregation-problem/483219/

America’s Health Segregation Problem

Has the country done enough to overcome its Jim Crow health care history?

VANN R. NEWKIRK II

MAY 18, 2016

Like other forms of segregation, health-care segregation was originally a function of explicitly racist black codes and Jim Crow laws. Many hospitals, clinics, and doctor’s offices were totally segregated by race, and many more maintained separate wings or staff that could never intermingle under threat of law. The deficit of trained black medical professionals (itself caused by a number of factors including education segregation) meant that no matter where black people received health-care services, they would find their care to be subpar compared to that of whites. While there were some deaths that were directly attributable to being denied emergency service, most of the damage was done in establishing the same cumulative health disparities that plague black people today as a societal fate. The descendants of enslaved people lived much more dangerous and unhealthy lives than white counterparts, on disease-ridden and degraded environments. Within the confines of a segregated health-care system, these factors became poor health outcomes that shaped black America as if they were its genetic material.

 

https://twitter.com/time4equity/status/1175080469425266688?s=20

 

R.A.HahnaB.I.TrumanbD.R.Williamsc.Civil rights as determinants of public health and racial and ethnic health equity: Health care, education, employment, and housing in the United States.

SSM – Population Health: Volume 4, April 2018, Pages 17-24

Highlights

  • Civil rights are characterized as social determinants of health.
  • Four domains in civil rights history since 1950 are explored in—health care, education, employment, and housing.
  • Health care, education, employment show substantial benefits when civil rights are enforced.
  • Housing shows an overall failure to enforce existing civil rights and persistent discrimination.
  • Civil rights and their enforcement may be considered a powerful arena for public health theorizing, research, policy, and action.

 

For more articles on COVID-19 Please go to our Coronovirus Portal

https://pharmaceuticalintelligence.com/coronavirus-portal/

 

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National Public Radio interview with Dr. Anthony Fauci on his optimism on a COVID-19 vaccine by early 2021

Reporter: Stephen J. Williams, PhD

Below I am giving a link to an important interview by NPR’s Judy Woodruff with Dr. Anthony Fauci on his thoughts regarding the recent spikes in cases, the potential for a COVID-19 vaccine by next year, and promising therapeutics in the pipeline.  The interview link is given below however I will summarize a few of the highlights of the interview.

 

Some notes on the interview

Judy Woodruff began her report with some up to date news regarding the recent spike and that Miami Florida has just ordered the additional use of facemasks.  She asked Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAD), about if the measures currently in use are enough to bring this spike down.  Dr. Fauci said that we need to reboot our efforts, mainly because people are not doing three things which could have prevented this spike mainly

  1. universal wearing of masks
  2. distancing properly from each other
  3. close the bars and pubs (see Wisconsin bars packed after ruling)

It hasn’t been a uniform personal effort

Dr. Fauci on testing

We have to use the tests we have out there efficiently and effectively And we have to get them out to the right people who can do the proper identification, isolation, and do proper contract tracing and need to test more widely in a surveillance way to get a feel of the extent and penetrance of this community spread.  there needs to be support and money for these testing labs

We have a problem and we need to admit and own it but we need to do the things we know are effective to turn this thing around.

On Vaccines

“May be later this year”

His response to Merck’s CEO Ken Frazer who said officials are giving false hop if they say ‘end of year’ but Dr. Fauci disagrees.  He says a year end goal is not outlandish.

What we have been doing is putting certain things in line with each other in an unprecedented way.

Dr. Fauci went on to say that, in the past yes, it took a long time, even years to develop a vaccine but now they have been able to go from sequence of virus to a vaccine development program in days, which is unheard of.  Sixty two days later we have gone into phase 1 trials. the speed at which this is occurring is so much faster.  He says that generally it would take a couple of years to get a neutralizing antibody but we are already there.  Another candidate will be undergoing phase 3 trials by end of this month (July 2020).

He is “cautiously optimistic” that we will have one or more vaccines to give to patients by end of year because given the amount of cases it will be able to get a handle on safety and efficacy by late fall.

Now he says the game changer is that the government is working with companies to ramp up the production of doses of the candidate vaccines so when we find which one works we will have ample doses on hand.  He is worried about the anti vaccine movement derailing vaccine testing and vaccinations but says if we keep on informing the public we can combat this.

Going back to school

Dr. Fauci is concerned for the safety of the vulnerable in schools, including students and staff.  He wants the US to get down to a reasonable baseline of cases but in the US that baseline after the first wave was still significantly higher than in most countries, where the baseline was more like tens of cases not hundreds of cases.

For more information on COVID-19 Please go to our Coronavirus Portal at

https://pharmaceuticalintelligence.com/coronavirus-portal/

 

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Placenta lacks molecules required for COVID-19 infection

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 10 million people, including pregnant women. To date, no consistent evidence for the vertical transmission of SARS-CoV-2 has been found. The placenta serves as the lungs, gut, kidneys, and liver of the fetus. This fetal organ also has major endocrine actions that modulate maternal physiology and, importantly, together with the extraplacental chorioamniotic membranes shield the fetus against microbes from hematogenous dissemination and from invading the amniotic cavity.

 

Most pathogens that cause hematogenous infections in the mother are not able to reach the fetus, which is largely due to the potent protective mechanisms provided by placental cells (i.e. trophoblast cells: syncytiotrophoblasts and cytotrophoblasts). Yet, some of these pathogens such as Toxoplasma gondii, Rubella virus, herpesvirus (HSV), cytomegalovirus (CMV), and Zika virus (ZIKV), among others, are capable of crossing the placenta and infecting the fetus, causing congenital disease.

 

The placental membranes that contain the fetus and amniotic fluid lack the messenger RNA (mRNA) molecule required to manufacture the ACE2 receptor, the main cell surface receptor used by the SARS-CoV-2 virus to cause infection. These placental tissues also lack mRNA needed to make an enzyme, called TMPRSS2, that SARS-CoV-2 uses to enter a cell. Both the receptor and enzyme are present in only miniscule amounts in the placenta, suggesting a possible explanation for why SARS-CoV-2 has only rarely been found in fetuses or newborns of women infected with the virus, according to the study authors.

 

The single-cell transcriptomic analysis presented by the researchers provides evidence that SARS-CoV-2 is unlikely to infect the placenta and fetus since its canonical receptor and protease, ACE2 and TRMPSS2, are only minimally expressed by the human placenta throughout pregnancy. In addition, it was shown that the SARS-CoV-2 receptors are not expressed by the chorioamniotic membranes in the third trimester. However, viral receptors utilized by CMV, ZIKV, and others are highly expressed by the human placental tissues.

 

Transcript levels do not always correlate with protein expression, but the data of the present study indicates a low likelihood of placental infection and vertical transmission of SARS-CoV-2. However, it is still possible that the expression of these proteins is much higher in individuals with pregnancy complications related with the renin-angiotensin-aldosterone system, which can alter the expression of ACE2. The cellular receptors and mechanisms that could be exploited by SARS-CoV-2 are still under investigation.

 

References:

 

https://www.nih.gov/news-events/news-releases/placenta-lacks-major-molecules-used-sars-cov-2-virus-cause-infection

 

https://pubmed.ncbi.nlm.nih.gov/32662421/

 

https://pubmed.ncbi.nlm.nih.gov/32217113/

 

https://pubmed.ncbi.nlm.nih.gov/32161408/

 

https://pubmed.ncbi.nlm.nih.gov/32335053/

 

https://pubmed.ncbi.nlm.nih.gov/32298273/

 

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The Global Economic Outlook During the COVID-19 Pandemic: A Changed World

Reporter: Joel Shertok, PhD

 

By the World Bank — June 8, 2020

https://www.worldbank.org/en/news/feature/2020/06/08/the-global-economic-outlook-during-the-covid-19-pandemic-a-changed-world

This is THE definitive assessment of the economic effects of COVID-19, from the World Bank. Obviously, bad and likely getting worse with the coming of the Second Lockdown……

Empty highway in Dubai because on coronavirus. Sign advertising the Stay Home Stay Safe campaign.

An empty highway in Dubai during the coronavirus pandemic. Above the highway, a sign reads “Stay Safe, Stay Home.” © Mo Azizi/Shutterstock


As the health and human toll grows, the economic damage is already evident and represents the largest economic shock the world has experienced in decades.

The June 2020 Global Economic Prospects describes both the immediate and near-term outlook for the impact of the pandemic and the long-term damage it has dealt to prospects for growth. The baseline forecast envisions a 5.2 percent contraction in global GDP in 2020, using market exchange rate weights—the deepest global recession in decades, despite the extraordinary efforts of governments to counter the downturn with fiscal and monetary policy support. Over the longer horizon, the deep recessions triggered by the pandemic are expected to leave lasting scars through lower investment, an erosion of human capital through lost work and schooling, and fragmentation of global trade and supply linkages.

For emerging market and developing countries, many of which face daunting vulnerabilities, it is critical to strengthen public health systems, address the challenges posed by informality, and implement reforms that will support strong and sustainable growth once the health crisis abates.

Historic contraction of per capita income

Advanced economies are projected to shrink 7 percent. That weakness will spill over to the outlook for emerging market and developing economies, who are forecast to contract by 2.5 percent as they cope with their own domestic outbreaks of the virus. This would represent the weakest showing by this group of economies in at least sixty years.


“The crisis highlights the need for urgent action to cushion the pandemic’s health and economic consequences, protect vulnerable populations, and set the stage for a lasting recovery.”


Every region is subject to substantial growth downgrades. East Asia and the Pacific will grow by a scant 0.5%. South Asia will contract by 2.7%, Sub-Saharan Africa by 2.8%, Middle East and North Africa by 4.2%, Europe and Central Asia by 4.7%, and Latin America by 7.2%.  These downturns are expected to reverse years of progress toward development goals and tip tens of millions of people back into extreme poverty.

Emerging market and developing economies will be buffeted by economic headwinds from multiple quarters: pressure on weak health care systems, loss of trade and tourism, dwindling remittances, subdued capital flows, and tight financial conditions amid mounting debt. Exporters of energy or industrial commodities will be particularly hard hit. Demand for metals and transport-related commodities such as rubber and platinum used for vehicle parts has also tumbled. While agriculture markets are well supplied globally, trade restrictions and supply chain disruptions could yet raise food security issues in some places.

A Worker in Sub-Saharan Africa standing near a truck is seen wearing a mask

A worker wears a mask in Sub-Saharan Africa. © Lucian Coman/Shutterstock

A possibility of even worse outcomes

Even this bleak outlook is subject to great uncertainty and significant downside risks. The forecast assumes that the pandemic recedes in such a way that domestic mitigation measures can be lifted by mid-year in advanced economies and later in developing countries, that adverse global spillovers ease during the second half of 2020, and that widespread financial crises are avoided. This scenario would envision global growth reviving, albeit modestly, to 4.2% in 2021.

However, this view may be optimistic. Businesses might find it hard to service debt, heightened risk aversion could lead to climbing borrowing costs, and bankruptcies and defaults could result in financial crises in many countries. Under this downside scenario, global growth could shrink by almost 8% in 2020.

Looking at the speed with which the crisis has overtaken the global economy may provide a clue to how deep the recession will be. The sharp pace of global growth forecast downgrades points to the possibility of yet further downward revisions and the need for additional action by policymakers in coming months to support economic activity.

A particularly concerning aspect of the outlook is the humanitarian and economic toll the global recession will take on economies with extensive informal sectors that make up an estimated one-third of the GDP and about 70% of total employment in emerging market and developing economies. Policymakers must consider innovative measures to deliver income support to these workers and credit support to these businesses.

Long-term damage to potential output, productivity growth

The June 2020 Global Economic Prospects looks beyond the near-term outlook to what may be lingering repercussions of the deep global recession: setbacks to potential output⁠—the level of output an economy can achieve at full capacity and full employment⁠—and labor productivity.  Efforts to contain COVID-19 in emerging and developing economies, including low-income economies with limited health care capacity, could precipitate deeper and longer recessions⁠—exacerbating a multi-decade trend of slowing potential growth and productivity growth.

Image

Another important feature of the current landscape is the historic collapse in oil demand and oil prices. Low oil prices are likely to provide, at best, temporary initial support to growth once restrictions to economic activity are lifted. However, even after demand recovers, adverse impacts on energy exporters may outweigh any benefits to activity in energy importers. In addition, the recent oil price plunge may provide further momentum to undertake energy subsidy reforms and deepen them once the immediate health crisis subsides.

In the face of this disquieting outlook, the immediate priority for policymakers is to address the health crisis and contain the short-term economic damage. Over the longer term, authorities need to undertake comprehensive reform programs to improve the fundamental drivers of economic growth once the crisis lifts.

, including support for the private sector and getting money directly to people. During the mitigation period, countries should focus on sustaining economic activity with support for households, firms and essential services.

Global coordination and cooperation—of the measures needed to slow the spread of the pandemic, and of the economic actions needed to alleviate the economic damage, including international support—provide the greatest chance of achieving public health goals and enabling a robust global recovery.

SOURCE

https://www.worldbank.org/en/news/feature/2020/06/08/the-global-economic-outlook-during-the-covid-19-pandemic-a-changed-world

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Reported by Joel Shertok, PhD,

From the New York Times, May 31, 2020

https://www.nytimes.com/2020/05/29/business/coronavirus-economic-forecast-shiller.html

By 

The Great Depression of the 1930s was an economic downturn that became a prolonged malaise. A Nobel laureate asks whether that pattern might be repeated.

Yogi Berra supposedly said, “It’s difficult to make predictions, especially about the future.” Yet, in spite of this warning, a cottage industry has arisen trying to anticipate the long term economics effects of the COVID-19 pandemic. Robert Schiller, Professor of Economics at Yale, in the NY Times, sounds a call for caution:

Longer-term analyses of the coronavirus pandemic emphasize that there is a good chance that it will fade within a year or two, especially if a vaccine or effective treatment appears.

I hope that’s true. But even if it is, I’m worried that the economy may not return to normal within that time frame.

Big events like a pandemic have the potential to leave behind a trail of disruption. They can create social discord, reduce people’s willingness to spend and take risks, destroy business momentum and shake confidence in the value of investments.

But episodes as far-reaching as this one are scarce, widely spaced in time, and so different in circumstances that statisticians cannot easily compare them systematically. The best we can do is examine some case studies.

The so-called Spanish flu, the influenza epidemic that started in 1918, which ultimately cost 675,000 American lives and millions around the world, is a reasonable place to start. While we know a great deal about that era, we don’t know enough to shed much light on current circumstances.

There was a recession in the United States from August 1918 to March 1919, according to the National Bureau of Economic Research, but not a deep one. Searching the newspapers of the time, one finds surprisingly little concern about the possible ill effects of the influenza on the economy, perhaps because the more-dominant narrative concerned the impact of World War I, which ended on November 11, 1918.

Yet a recent study by Robert Barro of Harvard University and his associates suggests that the epidemic along with the decline in production associated with the war led to a protracted decline in G.D.P. growth in affected countries from 1918 through 1920. In short, that period provides little comfort.

Perhaps more relevant to the current crisis is the Great Depression of 1929 to 1940, the biggest economic slowdown of modern history. From 1931 to 1940, the annual unemployment rate in the United States never fell below 12 percent. (In April this year, unemployment shot up to 14.7 percent.)

The conventional story is that the 1929 crash was the result of a stock market bubble in the 1920s. The Cyclically Adjusted Price Earnings Ratio, a stock valuation measure that I helped develop, reached 32.6 in 1929 (compared with 31.0 in January 2020). The Depression started in 1929 after a 23 percent crash in the Dow Jones industrial average over two days, Oct. 28 and 29. It created global social unrest around the world and the downturn only ended with World War II.

In 1929 many people expected the stock market to bounce right back and that decline was short-lived, in one sense: The market rose almost half the way back to its 1929 peak by April 1930. But it fell sharply again, and the crash set in motion a train of powerful narratives that resemble some of the popular notions that are circulating today.

Much as President Trump dismissed the seriousness of the Covid-19 pandemic in its early days, President Herbert Hoover made optimistic forecasts that proved to be wrong.

Much as people fret these days about extreme polarization between Democrats and Republicans, so too were people of that era concerned about extreme political divisiveness. After losing the 1932 election to Franklin Delano Roosevelt, for example, President Hoover, by then a lame duck, called F.D.R.’s plans a “march to Moscow.”

Much as people today have experienced long lines and empty shelves at supermarkets, in the Great Depression people fretted about long lines and empty cash registers at banks.

There are other troubling parallels: Fear of long-term unemployment and a never-ending depression was rampant back then, leading people to restrain spending, thus prolonging the downturn. This may not happen now, but it is a danger.

Much as now, in the Great Depression people were very focused on maintaining a “fair wage” in the face of economic distress. But this led to nationwide resistance to nominal wage cuts for anyone, even when retail prices were falling rapidly.

This appears to have had the unintended result of inducing employers, who could not afford to keep everyone working at their former wages, to lay off many people. The economists Harold L. Cole of the University of Pennsylvania and Lee E. Ohanian, of U.C.L.A., have shown that this may explain some of the extreme duration of Great Depression unemployment.

Another development back then may have resonance today. Faced with widespread poverty, even people with money voluntarily embraced austerity, saying they no longer needed to “keep up with the Joneses.” Their reduction in consumption helps to explain the severity and duration of the Depression. If contemporary culture shifts in a similar way, it could limit the economy’s ability to bounce back.

A series of concerns like these — some with echoes of the Great Depression, some newly forming and associated directly with worries about disease and infection — will be on millions of people’s minds long after the economy reopens. Such social narratives will affect their thinking on how to spend and invest, whether to go out to eat or attend sporting events, on whom to vote for, and whether to travel: multitudes of decisions, big and small, that determine the course of the economy.

It is too early to tell which narratives will prevail and what path the economy will take after this pandemic subsides. Limited case studies will take us only so far. But we shouldn’t be surprised if we see post-pandemic economic weakness over the next decade.

SOURCE

https://www.nytimes.com/2020/05/29/business/coronavirus-economic-forecast-shiller.html

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From Cell Press:  New Insights on the D614G Strain of COVID: Will a New Mutated Strain Delay Vaccine Development?

Reporter: Stephen J. Williams, PhD

Two recent articles in Cell Press, both peer reviewed, discuss the emergence and potential dominance of a new mutated strain of COVID-19, in which the spike protein harbors a D614G mutation.

In the first article “Making Sense of Mutation: What D614G means for the COVID-19 pandemic Remains Unclear”[1] , authors Drs. Nathan Grubaugh, William Hanage, and Angela Rasmussen discuss the recent findings by Korber et al. 2020 [2] which describe the potential increases in infectivity and mortality of this new mutant compared to the parent strain of SARS-CoV2.  For completeness sake I will post this article as to not defer from their interpretations of this important paper by Korber and to offer some counter opinion to some articles which have surfaced this morning in the news.

Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear

 

Nathan D. Grubaugh1 *, William P. Hanage2 *, Angela L. Rasmussen3 * 1Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA 2Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA 3Center for Infection and Immunity, Columbia Mailman School of Public Health, New York, NY 10032, USA Correspondence: grubaughlab@gmail.com

 

Abstract: Korber et al. (2020) found that a SARS-CoV-2 variant in the spike protein, D614G, rapidly became dominant around the world. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.

Introduction: Following the emergence of SARS-CoV-2 in China in late 2019, and the rapid expansion of the COVID19 pandemic in 2020, questions about viral evolution have come tumbling after. Did SARS-CoV-2 evolve to become better adapted to humans? More infectious or transmissible? More deadly? Virus mutations can rise in frequency due to natural selection, random genetic drift, or features of recent epidemiology. As these forces can work in tandem, it’s often hard to differentiate when a virus mutation becomes common through fitness or by chance. It is even harder to determine if a single mutation will change the outcome of an infection, or a pandemic. The new study by Korber et al. (2020) sits at the heart of this debate. They present compelling data that an amino acid change in the virus’ spike protein, D614G, emerged early during the pandemic, and viruses containing G614 are now dominant in many places around the world. The crucial questions are whether this is the result of natural selection, and what it means for the COVID-19 pandemic. For viruses like SARS-CoV-2 transmission really is everything – if they don’t get into another host their lineage ends. Korber et al. (2020) hypothesized that the rapid spread of G614 was because it is more infectious than D614. In support of their hypothesis, the authors provided evidence that clinical samples from G614 infections have a higher levels of viral RNA, and produced higher titers in pseudoviruses from in vitro experiments; results that now seem to be corroborated by others [e.g. (Hu et al., 2020; Wagner et al., 2020)]. Still, these data do not prove that G614 is more infectious or transmissible than viruses containing D614. And because of that, many questions remain on the potential impacts, if any, that D614G has on the COVID-19 pandemic.

The authors note that this new G614 variant has become the predominant form over the whole world however in China the predominant form is still the D614 form.  As they state

“over the period that G614 became the global majority variant, the number of introductions from China where D614 was still dominant were declining, while those from Europe climbed. This alone might explain the apparent success of G614.”

Grubaugh et al. feel there is not enough evidence that infection with this new variant will lead to higher mortality.  Both Korber et al. and the Seattle study (Wagner et al) did not find that the higher viral load of this variant led to a difference in hospitalizations so apparently each variant might be equally as morbid.

In addition, Grubaugh et al. believe this variant would not have much affect on vaccine development as, even though the mutation lies within the spike protein, D614G is not in the receptor binding domain of the spike protein.  Korber suggest that there may be changes in glycosylation however these experiments will need to be performed.  In addition, antibodies from either D614 or G614 variant infected patients could cross neutralize.

 

Conclusions: While there has already been much breathless commentary on what this mutation means for the COVID19 pandemic, the global expansion of G614 whether through natural selection or chance means that this variant now is the pandemic. As a result its properties matter. It is clear from the in vitro and clinical data that G614 has a distinct phenotype, but whether this is the result of bonafide adaptation to human ACE2, whether it increases transmissibility, or will have a notable effect, is not clear. The work by Korber et al. (2020) provides an early base for more extensive epidemiological, in vivo experimental, and diverse clinical investigations to fill in the many critical gaps in how D614G impacts the pandemic.

The link to the Korber Cell paper is here: https://www.cell.com/cell/fulltext/S0092-8674(20)30820-5

Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

DOI: https://doi.org/10.1016/j.cell.2020.06.043

Keypoints

  • The consistent increase of G614 at regional levels may indicate a fitness advantage

 

  • G614 is associated with lower RT PCR Ct’s, suggestive of higher viral loads in patients

 

  • The G614 variant grows to higher titers as pseudotyped virions

Summary

A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.

 

References

  1. Grubaugh, N.D., Hanage, W.P., Rasmussen, A.L., Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear, Cell (2020), doi: https:// doi.org/10.1016/j.cell.2020.06.040.
  2. Korber, B., Fischer, W.M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E.E., Bhattacharya, T., Foley, B., et al. (2020). Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182.
  3. Endo, A., Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott, S., Kucharski, A.J., and Funk, S. (2020). Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China. Wellcome Open Res 5, 67.
  4. Hu, J., He, C.-L., Gao, Q.-Z., Zhang, G.-J., Cao, X.-X., Long, Q.-X., Deng, H.-J., Huang, L.-Y., Chen, J., Wang, K., et al. (2020). The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera. bioRxiv 2020.06.20.161323.
  5. Wagner, C., Roychoudhury, P., Hadfield, J., Hodcroft, E.B., Lee, J., Moncla, L.H., Müller, N.F., Behrens, C., Huang, M.-L., Mathias, P., et al. (2020). Comparing viral load and clinical outcomes in Washington State across D614G mutation in spike protein of SARS-CoV-2. Https://github.com/blab/ncov-D614G.

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6/30/2020

Chasing change: Innovation and patent
activity during COVID-19

A report on the pandemic’s impact on the global
R&D community and innovation lifecycle

Reporters: Aviva Lev-Ari, Ph.D., RN & Gail S. Thornton, M.A.

Published by Clarivate Derwent

In just a few short months, COVID-19 swept through the world. While many aspects of everyday life have altered as the pandemic has gripped the globe, society at large has been and remains remarkably resilient.

To understand the impact of COVID-19 on the world’s innovators, we asked organizations from a cross-section of industries globally about how the pandemic has affected their organizations’ innovation strategies.

We are pleased to share the results with you in the report, “Chasing change: Innovation and patent activity during COVID-19.”

SOURCE:

https://clarivate.com/derwent/wp-content/uploads/sites/3/dlm_uploads/2020/06/DW507408683-COVID-19-Report_FINAL.pdf?utm_campaign=EM1_Report_Derwent_COVID_19_Survey_Apr_IPS_Global_2020_ClientsProspects

Other related article published in this Open Access Online Scientific Journal include the following:

Corticosteroid, Dexamethasone Improves Survival in COVID-19: Deaths reduction by 1/3 in ventilated patients and by 1/5 in other patients receiving oxygen only

Reporter: Aviva Lev-Ari, PhD, RN https://pharmaceuticalintelligence.com/2020/06/27/corticosteroid-dexamethasone-improves-survival-in-covid-19-deaths-reduction-by-1-3-in-ventilated-patients-and-by-1-5-in-other-patients-receiving-oxygen-only/

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6/30/2020

Innovation and Patent Activity during COVID-19 from Clarivate – Survey Results Published

Reporter: Aviva Lev-Ari, PhD, RN & Gail S. Thornton, M.A.

From: Vashe Kanesarajah <news@mail.discover.clarivate.com>

Reply-To: Derwent <news@clarivate.com>

Date: Tuesday, June 30, 2020 at 10:01 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Now available: Innovation and patent activity during COVID-19

Download the survey results
View online
COVID-19’s impact on global innovation
 
Download the survey results
Chasing change: Innovation and patent activity during COVID-19
Dear Colleague,

 

In just a few short months, COVID-19 swept through the world. While many aspects of everyday life have altered as the pandemic has gripped the globe, society at large has been and remains remarkably resilient.

To understand the impact of COVID-19 on the world’s innovators, we asked organizations from a cross-section of industries globally about how the pandemic has affected their organizations’ innovation strategies. We are pleased to share the results with you in the report, Chasing change: Innovation and patent activity during COVID-19.” I hope you find it insightful.

Warm regards,

Vashe Kanesarajah
Head of Strategic Development, IP Group
Clarivate

 

Other related article published in this Open Access Online Scientific Journal include the following:

Corticosteroid, Dexamethasone Improves Survival in COVID-19: Deaths reduction by 1/3 in ventilated patients and by 1/5 in other patients receiving oxygen only

Reporter: Aviva Lev-Ari, PhD, RN 

https://pharmaceuticalintelligence.com/2020/06/27/corticosteroid-dexamethasone-improves-survival-in-covid-19-deaths-reduction-by-1-3-in-ventilated-patients-and-by-1-5-in-other-patients-receiving-oxygen-only/

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The Complexity of Estimation of the Economic Impact of an Outbreak | Panel Discussion | BC Woods College

Reporter: Ofer Markman, PhD

Economic Impact of an Outbreak | Panel Discussion | BC Woods College

197 views

May 21, 2020

Prominent economists, all faculty of the Boston College M.S. in Applied Economics degree program in the Woods College of Advancing Studies, presented a virtual panel discussion on the impact of the coronavirus outbreak on the health care system and the global economy. For more information about the M.S. program, visit https://on.bc.edu/MSAppliedEcon

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A Series of Recently Published Papers Report the Development of SARS-CoV2 Neutralizing Antibodies and Passive Immunity toward COVID19

Curator: Stephen J. Williams, Ph.D.

 

Passive Immunity and Treatment of Infectious Diseases

The ability of one person to pass on immunity to another person (passive immunity) is one of the chief methods we develop immunity to many antigens.  For instance, maternal antibodies are passed to the offspring in the neonatal setting as well as in a mother’s milk during breast feeding.  In the clinical setting this is achieved by transferring antibodies from one patient who has been exposed to an antigen (like a virus) to the another individual.   However, the process of purifying the most efficacious antibody as well as its mass production is limiting due to its complexity and cost and can be prohibitively long delay during a pandemic outbreak, when therapies are few and needed immediately.  Regardless, the benefits of developing neutralizing antibodies to confer passive immunity versus development of a vaccine are evident, as the former takes considerable less time than development of a safe and effective vaccine.  For a good review on the development and use of neutralizing antibodies and the use of passive immunity to treat infectious diseases please read the following review:

Margaret A. Keller1,* and E. Richard Stiehm. Passive Immunity in Prevention and Treatment of Infectious Diseases. Clin Microbiol Rev. 2000 Oct; 13(4): 602–614. doi: 10.1128/cmr.13.4.602-614.2000

ABSTRACT

Antibodies have been used for over a century in the prevention and treatment of infectious disease. They are used most commonly for the prevention of measles, hepatitis A, hepatitis B, tetanus, varicella, rabies, and vaccinia. Although their use in the treatment of bacterial infection has largely been supplanted by antibiotics, antibodies remain a critical component of the treatment of diptheria, tetanus, and botulism. High-dose intravenous immunoglobulin can be used to treat certain viral infections in immunocompromised patients (e.g., cytomegalovirus, parvovirus B19, and enterovirus infections). Antibodies may also be of value in toxic shock syndrome, Ebola virus, and refractory staphylococcal infections. Palivizumab, the first monoclonal antibody licensed (in 1998) for an infectious disease, can prevent respiratory syncytial virus infection in high-risk infants. The development and use of additional monoclonal antibodies to key epitopes of microbial pathogens may further define protective humoral responses and lead to new approaches for the prevention and treatment of infectious diseases.

TABLE 1

Summary of the efficacy of antibody in the prevention and treatment of infectious diseases

Infection
Bacterial infections
 Respiratory infections (streptococcus, Streptococcus pneumoniaeNeisseria meningitisHaemophilus influenzae)
 Diphtheria
 Pertussis
 Tetanus
 Other clostridial infections
  C. botulinum
  C. difficile
 Staphylococcal infections
  Toxic shock syndrome
  Antibiotic resistance
  S. epidermidis in newborns
 Invasive streptococcal disease (toxic shock syndrome)
 High-risk newborns
 Shock, intensive care, and trauma
Pseudomonas infection
  Cystic Fibrosis
  Burns
Viral diseases
 Hepatitis A
 Hepatitis B
 Hepatitis C
 HIV infection
 RSV infection
 Herpesvirus infections
  CMV
  EBV
  HSV
  VZV
 Parvovirus infection
 Enterovirus infection
  In newborns
 Ebola
 Rabies
 Measles
 Rubella
 Mumps
 Tick-borne encephalitis
 Vaccinia

Go to:

A Great Explanation of Active versus Passive Immunity by Dr. John Campbell, one of the pioneers in the field of immunology:Antibodies have been used for over a century in the prevention and treatment of infectious disease. They are used most commonly for the prevention of measles, hepatitis A, hepatitis B, tetanus, varicella, rabies, and vaccinia. Although their use in the treatment of bacterial infection has largely been supplanted by antibiotics, antibodies remain a critical component of the treatment of diptheria, tetanus, and botulism. High-dose intravenous immunoglobulin can be used to treat certain viral infections in immunocompromised patients (e.g., cytomegalovirus, parvovirus B19, and enterovirus infections). Antibodies may also be of value in toxic shock syndrome, Ebola virus, and refractory staphylococcal infections. Palivizumab, the first monoclonal antibody licensed (in 1998) for an infectious disease, can prevent respiratory syncytial virus infection in high-risk infants. The development and use of additional monoclonal antibodies to key epitopes of microbial pathogens may further define protective humoral responses and lead to new approaches for the prevention and treatment of infectious diseases.

 

However, developing successful neutralizing antibodies can still be difficult but with the latest monoclonal antibody technology, as highlighted by the following papers, this process has made much more efficient.  In addition, it is not feasable to isolate antibodies from the plasma of covalescent patients in a scale that is needed for a worldwide outbreak.

A good explanation of the need can be found is Dr. Irina Robu’s post Race to develop antibody drugs for COVID-19 where:

When fighting off foreign invaders, our bodies make antibodies precisely produced for the task. The reason vaccines offer such long-lasting protection is they train the immune system to identify a pathogen, so immune cells remember and are ready to attack the virus when it appears. Monoclonal antibodies for coronavirus would take the place of the ones our bodies might produce to fight the disease. The manufactured antibodies would be infused into the body to either tamp down an existing infection, or to protect someone who has been exposed to the virus. However, these drugs are synthetic versions of the convalescent plasma treatments that rely on antibodies from people who have recovered from infection. But the engineered versions are easier to scale because they’re manufactured in rats, rather than from plasma donors.

The following papers represent the latest published work on development of therapeutic and prophylactic neutralizing antibodies to the coronavirus SARS-CoV2

1.  Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody.

Pinto, D., Park, Y., Beltramello, M. et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature (2020).                                                                            https://doi.org/10.1038/s41586-020-2349-y

Abstract

SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than 3.7 million infections and 260,000 deaths as of 6 May 20201,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of an individual who was infected with SARS-CoV in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309- and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.

 

2.  Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells

Yunlong Cao et al.  Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell (2020).

https://doi.org/10.1016/j.cell.2020.05.025

Summary

The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here we report the rapid identification of SARS-CoV-2 neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1+ clonotypes, 14 potent neutralizing antibodies were identified with the most potent one, BD-368-2, exhibiting an IC50 of 1.2 ng/mL and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8Å Cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody’s epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2 neutralizing antibodies could be directly selected based on similarities of their predicted CDR3H structures to those of SARS-CoV neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B-cell sequencing in response to pandemic infectious diseases.

3. A human monoclonal antibody blocking SARS-CoV-2 infection

Wang, C., Li, W., Drabek, D. et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun 11, 2251 (2020). https://doi.org/10.1038/s41467-020-16256-y

Abstract

The emergence of the novel human coronavirus SARS-CoV-2 in Wuhan, China has caused a worldwide epidemic of respiratory disease (COVID-19). Vaccines and targeted therapeutics for treatment of this disease are currently lacking. Here we report a human monoclonal antibody that neutralizes SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targets a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19.

Extra References on Development of Neutralizing antibodies for COVID19 {Sars-CoV2} published this year (2020)  [1-4]

  1. Fan P, Chi X, Liu G, Zhang G, Chen Z, Liu Y, Fang T, Li J, Banadyga L, He S et al: Potent neutralizing monoclonal antibodies against Ebola virus isolated from vaccinated donors. mAbs 2020, 12(1):1742457.
  2. Dussupt V, Sankhala RS, Gromowski GD, Donofrio G, De La Barrera RA, Larocca RA, Zaky W, Mendez-Rivera L, Choe M, Davidson E et al: Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor. Nature medicine 2020, 26(2):228-235.
  3. Young CL, Lyons AC, Hsu WW, Vanlandingham DL, Park SL, Bilyeu AN, Ayers VB, Hettenbach SM, Zelenka AM, Cool KR et al: Protection of swine by potent neutralizing anti-Japanese encephalitis virus monoclonal antibodies derived from vaccination. Antiviral research 2020, 174:104675.
  4. Sautto GA, Kirchenbaum GA, Abreu RB, Ecker JW, Pierce SR, Kleanthous H, Ross TM: A Computationally Optimized Broadly Reactive Antigen Subtype-Specific Influenza Vaccine Strategy Elicits Unique Potent Broadly Neutralizing Antibodies against Hemagglutinin. J Immunol 2020, 204(2):375-385.

 

For More Articles on COVID-19 Please see Our Coronavirus Portal on this Open Access Scientific Journal at:

https://pharmaceuticalintelligence.com/coronavirus-portal/

and the following Articles on  Immunity at

Race to develop antibody drugs for COVID-19
Bispecific and Trispecific Engagers: NK-T Cells and Cancer Therapy
Issues Need to be Resolved With ImmunoModulatory Therapies: NK cells, mAbs, and adoptive T cells
Antibody-bound Viral Antigens

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