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COVID-19 case severity: How genetic differences leave immune cells at a disadvantage

LA JOLLA, CA—New research shows how genetic variations linked to severe cases of COVID-19 affect our immune cells. Credit: La Jolla Institute for Immunology LA JOLLA, CA—New research shows how genetic variations linked to severe cases of COVID-19…

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LA JOLLA, CA—New research shows how genetic variations linked to severe cases of COVID-19 affect our immune cells.

Credit: La Jolla Institute for Immunology

LA JOLLA, CA—New research shows how genetic variations linked to severe cases of COVID-19 affect our immune cells.

The study, led by scientists at La Jolla Institute for Immunology (LJI), is one of the first in-depth look at the connections between COVID-19 severity and gene expression in many types of immune cells. This work could guide the development of new COVID-19 therapies to boost immune cell function.

Among their findings, the researchers report that a gene in a cell type called non-classical monocytes, which are part of the body’s “first responder” team of innate immune cells, could be a potential target for COVID-19 therapies.

“This study highlights the power of human genetics to uncover novel pathways linked to disease,” says LJI Professor Pandurangan Vijayanand, M.D., Ph.D., senior author of the Nature Communications study.

The science community has identified many genetic differences, called polymorphisms, they call “severe COVID-19-risk variants.” These genetic variants are associated with gene expression and appear to influence case severity. Yet scientists didn’t know which immune cells are most affected by these risk variants.

For the new study, Vijayanand and his colleagues combined patient genetic data from the COVID-19 Host Genetic Initiative and LJI’s open-access Database of Immune Cell Epigenomes (DICE) to define the genes and susceptible cell types affected by these risk variants. The team looked at 13 subtypes of the body’s key protective and virus-fighting cells: T cells, B cells, NK cells and monocytes.

“There are many different immune cell types, and they all contribute small functions to the global picture,” says study first author Benjamin Schmiedel, Ph.D., an instructor at LJI. “We have to look at every immune cell type separately to figure out how the immune system is able to respond to COVID.”

The researchers identified several important associations of genetic variants with genes. Among them was a risk variant that affected 12 of the 13 cell types studied. This severe COVID-19-risk variant in chromosome 21 was associated with reduced expression of a receptor on cells called IFNAR2. This receptor is part of a signaling pathway that alerts the immune system to infection. This new association may help explain why some people fail to mount a strong immune response to SARS-CoV-2.

Meanwhile, a risk variant on chromosome 12 displayed the strongest effect in non-classical monocytes, a type of innate immune cell that patrols the body and sends signaling molecules to alert other immune cells to threats. The risk variant led non-classical monocytes to reduce expression of a gene called OAS1. A lack of OAS1 expression could hobble the body’s defenses by reducing the expression of a family of proteins that normally degrades viral RNA and activates the immune system’s antiviral responses.

“Non-classical monocytes are a rare, understudied cell type,” says Schmiedel. “They only make up about two percent of immune cells.”

Schmiedel hopes to conduct further pre-clinical assessments to determine the role of these genes in COVID-19 pathogenesis. “That we can identify these kinds of genetic mechanisms is a big step forward,” he says. “We can use the information out there, combine it with our data on immune cells, and find potential targets for therapy.”

Additional authors of the study, “COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types,” include Job Rocha, Cristian Gonzalez-Colin, Sourya Bhattacharyya, Ariel Madrigal, Christian H. Ottensmeier, Ferhat Ay and Vivek Chandra.

The study was supported by the National Institute of Health (grants R24-AI108564, R35-GM128938, S10RR027366, S10OD016262 and S10OD025052) and the William K. Bowes Jr. Foundation.

DOI: 10.1038/s41467-021-26888-3

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About La Jolla Institute for Immunology

The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease.

 


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Economics

FT-IGM US Macroeconomists Survey for December

The FT-IGM US Macroeconomists survey is out (it was conducted over the weekend). The results are summarized here, and an FT article here (gated). Here’s some of the results. For GDP, assuming Q4 is as predicted in the November Survey of Professional…

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The FT-IGM US Macroeconomists survey is out (it was conducted over the weekend). The results are summarized here, and an FT article here (gated). Here’s some of the results.

For GDP, assuming Q4 is as predicted in the November Survey of Professional Forecasters, we have the following picture.

Figure 1: GDP (black), potential GDP (gray), November Survey of Professional Forecasters (red), November SPF subtracting 1.5ppts in Q1, 05ppts in Q2 (blue), FT-IGM December survey (sky blue squares), all on log scale. FT-IGM GDP level assumes 2021Q4 growth rate equals SPF November forecast. NBER defined recession dates peak-to-trough shaded gray. Source: BEA 2021Q3 2nd release, Philadelphia Fed November SPF, FT-IGM December survey, and author’s calculations.

In the figure above, I’ve used the SPF forecast of 4.6% SAAR in 2021Q4; the Atlanta Fed’s nowcast as of yesterday (12/7) was 8.6% SAAR. A new nowcast comes out tomorrow.

Interestingly, q4/q4 median forecasted growth equals that implied by the Survey of Professional Forecasters November survey (which was taken nearly a month before news of the omicron variant came out).

The q4/q4 forecast distribution for 2022 is skewed, with the 90th percentile at 5% growth, the 10th percentile at 2.5%, and median at 3.5%. I show the corresponding implied levels of GDP (once again assuming 2021Q4 growth equals the SPF ).

Figure 2: GDP (black), November Survey of Professional Forecasters (red), FT-IGM December survey (sky blue squares), 90th percentile and 10th percentile implied levels (light blue +), my median forecast (green triangle), all on log scale. FT-IGM GDP level assumes 2021Q4 growth rate equals SPF November forecast. NBER defined recession dates peak-to-trough shaded gray. Source: BEA 2021Q3 2nd release, Philadelphia Fed November SPF, FT-IGM December survey, and author’s calculations.

On unemployment, the median forecast is for a deceleration in recovery,

Figure 3: Unemployment rate (black), November Survey of Professional Forecasters (red), FT-IGM December survey (sky blue square), 90th percentile and 10th percentile implied levels (light blue +), my median forecast (green triangle). NBER defined recession dates peak-to-trough shaded gray. Source: BEA 2021Q3 2nd release, Philadelphia Fed November SPF, FT-IGM December survey, and author’s calculations.

The survey respondents also think that the participation rate will take a long time to return to pre-pandemic levels.

Source: FT-IGM, December 2021 survey.

On inflation, the median is higher than the November SPF mean estimate for 2022 of 2.3% (and Goldman Sachs’ current estimate).

Source: FT-IGM, December 2021 survey.

The entire survey results are here.

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Government

Over 170 companies delisted from major U.S. stock exchanges in 12 months

  Over the years, United States-based exchanges have remained an attractive destination for most companies aiming to go public. With businesses jostling to join the trading platforms, the exchanges have also delisted a significant number of companies….

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Over the years, United States-based exchanges have remained an attractive destination for most companies aiming to go public. With businesses jostling to join the trading platforms, the exchanges have also delisted a significant number of companies.

According to data acquired by Finbold, a total of 179 companies have been delisted from the major United States exchanges between 2020 and 2021. In 2021, the number of companies on Nasdaq and the New York Stock Exchange (NYSE) stands at 6,000, dropping 2.89% from last year’s figure of 6,179. In 2019, the listed companies stood at 5,454.

NYSE recorded the highest delisting with companies on the platform, dropping 15.28% year-over-year from 2,873 to 2,434. Elsewhere, Nasdaq listed companies grew 7.86% from 3,306 to 3,566. Data on the number of listed companies on NASDAQ and NYSE is provided by The World Federation of Exchanges.

The delisting of the companies is potentially guided by basic factors such as violating listing regulations and failing to meet minimum financial standards like the inability to maintain a minimum share price, financial ratios, and sales levels. Additionally, some companies might opt for voluntary delisting motivated by the desire to trade on other exchanges.

Furthermore, the delisting on U.S. major exchanges might be due to the emergence of new alternative markets, especially in Asia. China and Hong Kong markets have become more appealing, with regulators making local listings more attractive. Over the years, exchanges in the region have strived to emerge as key players amid dominance by U.S. equity markets. As per a previous report, the U.S. controls 56% of the global stock market value.

A significant portion of the delisted companies also stems from the regulatory perspective pitting U.S. agencies and their Chinese counterparts. For instance, China Mobile Ltd, China Unicom, and China Telecom Corp announced their delisting from NYSE, citing investment restrictions dating from 2020.

Worth noting is that the delisting of firms was initiated due to strict measures put in place by the Trump administration. The current administration has left the regulations in place while proposing additional regulations. For instance, a recent regulation update by the Securities Exchange Commission requiring US-listed Chinese companies to disclose their ownership structure has led to the exit of cab-hailing company Didi from the NYSE.

Impact of pandemic on the listing of companies

The delisting also comes in the wake of the Covid-19 pandemic that resulted in economic turmoil. With the shutdown of the economy, most companies entered into bankruptcies as the stock market crashed to historical lows.

Lower stock prices translate to less wealth for businesses, pension funds, and individual investors, and listed companies could not get the much-needed funding for their normal operations.

At the same time, the focus on more companies going public over the last year can be highlighted by firms on the Nasdaq exchange. Worth noting is that in 2020, there was tremendous growth in special purpose acquisition companies (SPACs), mainly driven by the impact of the coronavirus pandemic. With the uncertainty of raising money through the traditional means, SPACs found a perfect role to inject more funds into capital-starving companies to go public.

From the data, foreign companies listing in the United States have grown steadily, with the business aiming to leverage the benefits of operating in the country. Notably, listing on U.S. exchanges guarantees companies liquidity and high potential to raise capital. Furthermore, listing on either NYSE or Nasdaq comes with the needed credibility to attract more investors. The companies are generally viewed as a home for established, respected, and successful global companies.

In general, over the past year, factors like the pandemic have altered the face of stock exchanges to some point threatening the continued dominance of major U.S. exchanges. Tensions between the US and China are contributing to the crisis which will eventually impact the number of listed companies.

 

Courtesy of Finbold.

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Economics

Stock futures open flat as Omicron concerns ease

Dow futures edged up 0.02%, while contracts on the Nasdaq Composite inched up 0.10%…
The post Stock futures open flat as Omicron concerns ease first appeared on Trading and Investment News.

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Dow futures edged up 0.02%, while contracts on the Nasdaq Composite inched up 0.10%

Stock futures opened relatively flat on Wednesday evening, though sustaining gains posted by a three-day recovery rally that was led by cooled investor concerns around the Omicron variant of the coronavirus.

Dow futures edged up 0.02%, while contracts on the tech-focused Nasdaq Composite inched up 0.10%. All major indexes closed up, with the S&P 500 adding 14.46 points to end the session at 4,701.21, just 0.5% short of the trading session on Nov. 24, a day before the latest COVID-19 variant was announced by the World Health Organization (WHO).

The moves were supported by eased virus fears after Pfizer Inc. and BioNTech reported that early lab studies show a third dose of their coronavirus vaccine mitigates the Omicron variant.

The vaccine makers had indicated the initial two doses may not be enough to protect against infection from Omicron. Shares of Pfizer (PFE) traded 0.62% lower on Wednesday, closing at $51.40.

With virus concerns diminishing, investors are pivoting their attention back to economic data, awaiting Consumer Price Index (CPI) figures on Friday to assess the extent inflationary pressures will persist.

If the Omicron variant was to lead to a resurgence in goods spending at the expense of services or to further complicate supply disruptions, there could be a clear inflationary impact, too, HSBC economist James Pomeroy wrote earlier this week in a research note to clients.

He stated: The inflation news in the past few weeks has been decidedly mixed — with upside surprises in both the U.S. and eurozone being offset by the possibility of some of the supply chain issues starting to alleviate, while energy prices have fallen sharply in recent days.

The post Stock futures open flat as Omicron concerns ease first appeared on Trading and Investment News.

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