Unique stem cell trajectory in lungs damaged by COVID-19 and pulmonary fibrosis

 Severe injuries to the lung from diseases such as COVID-19 trigger abnormal stem cell repair that alters the architecture of the lung. The aberrant stem cell differentiation in response to injury can prevent the restoration of normal lung function.  

In a collaborative study between UCSF researchers appearing December 30 in Nature Cell Biology, UCSF researchers Jaymin Kathiriya, PhD, and Chaoqun Wang, PhD, discovered that severe lung injuries can trigger lung stem cells to undergo abnormal differentiation. Drs. Kathiriya and Wang, supervised by Hal Chapman, MD, and Tien Peng, MD, respectively, utilized stem cell organoid models to uncover a novel stem cell pathway that is seen in severely injured lungs from COVID-19 and idiopathic pulmonary fibrosis patients.  

This study offers a roadmap to understand how severely injured lungs can remodel and scar and provides a potential pathway to reverse the remodeling by targeting the abnormal stem cells differentiation.  

It has been previously accepted that the regenerative capacity of resident stem cells of the alveolus (AEC2s), operates similarly mice and humans. The researchers unexpectedly found that human AEC2s (hAEC2s), unlike mouse AEC2s, robustly transdifferentiate into functional basal cells with cues from pathological fibroblasts. Single-cell analysis of the hAEC2-to-basal cell trajectory in vitro revealed the presence of transitional cell types and basal cell subsets previously identified in lungs with Idiopathic Pulmonary Fibrosis (IPF).  

Utilizing a novel fibroblast/hAEC2 organoid platform, the authors could model the stem cell metaplasia, or abnormal stem cell differentiation, seen in severe alveolar injury. Furthermore, the discovery that hAEC2s can generate pathologic transitional cell types and basal cells provides experimental confirmation of a stem cell trajectory that is seen in diseased human lungs. 

"The first time we saw hAEC2s differentiating into basal cells, it was so striking that we thought it was an error,” said Peng. “But rigorous validation of this novel trajectory has provided enormous insight on how the lung remodels in response to severe injury, and a potential path to reverse the damage." 

The finding that hAEC2s undergo progressive transdifferentiation to metaplastic basal cells is not unique to IPF. Alveolar metaplastic basal cells are also common in sections of scleroderma and COVID lungs, and these are intermingled with transitional cells in areas of active remodeling. The common finding of transitional cells in hAEC2-derived organoids as well as hAEC2 xenografts and in histologic analyses of fibrotic lungs, suggest hAEC2s are a major source of metaplastic basal cells in diseases with severe alveolar injury.  

The study provides the groundwork for future research to identify therapeutic targets that might prevent or reverse metaplastic differentiation in severe lung injury, and whether other components of the fibrotic niche such as endothelial cells and immune cells are able to drive the metaplastic phenotype. 

About UCSF Health: UCSF Health is recognized worldwide for its innovative patient care, reflecting the latest medical knowledge, advanced technologies and pioneering research. It includes the flagship UCSF Medical Center, which is ranked among the top 10 hospitals nationwide; as well as UCSF Benioff Children’s Hospitals, with campuses in San Francisco and Oakland; Langley Porter Psychiatric Hospital and Clinics; UCSF Benioff Children’s Physicians; and the UCSF Faculty Practice. These hospitals serve as the academic medical center of the University of California, San Francisco, which is world-renowned for its graduate-level health sciences education and biomedical research. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area 

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Follow UCSF: ucsf.edu | Facebook.com/ucsf | Twitter.com/ucsf | YouTube.com/ucsf 

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JOURNAL

Nature Cell Biology

DOI

10.1038/s41556-021-00809-4 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Lab-produced tissue samples

ARTICLE TITLE

Human alveolar type 2 epithelium transdifferentiates into metaplastic KRT5+ basal cells

ARTICLE PUBLICATION DATE

30-Dec-2021

https://www.eurekalert.org/news-releases/939077

UK government seeks to mitigate workforce disruption from Omicron

 

The British government has asked public sector managers to test their contingency plans against a worst-case scenario of 25% staff absence as part of efforts to minimise disruption from the rapid spread of the Omicron variant of COVID-19.

With daily infection numbers at a record high and people who test positive required to self-isolate for at least seven days, the government expects businesses and public services to face disruption in the coming weeks, it said in a statement.

"So far, disruption caused by Omicron has been controlled in most parts of the public sector, but public sector leaders have been asked to test plans against worst case scenarios of workforce absence of 10%, 20% and 25%," it said.

Prime Minister Boris Johnson has asked ministers to work closely with their respective sectors to develop robust contingency plans, said the Cabinet Office, which is coordinating the government's efforts.

The impact of Omicron on workforces in supply chains, public services and schools is being closely monitored, it said. Mitigations being considered include asking for volunteers such as retired teachers to go back to work.

"There is work ongoing to identify potential regulatory, policy or operational changes which could minimise or alleviate potential disruption," the Cabinet Office said.

The daily number of new COVID-19 infections across the United Kingdom rose to a record 189,846 on Friday, far higher than during previous peaks.

However, hospitalisations and deaths have remained at much lower levels than in previous waves.

https://www.marketscreener.com/news/latest/UK-government-seeks-to-mitigate-workforce-disruption-from-Omicron--37449688/

China ends 2021 with worst COVID week since taming original epidemic

 

China ended its final week of 2021 with its biggest tally of local coronavirus cases for any seven-day period since subduing the country's first epidemic nearly two years ago, despite an arsenal of some of the world's toughest COVID-19 measures.

The National Health Commission reported on Saturday 175 new community infections with confirmed clinical symptoms for Dec. 31, bringing the total number of local symptomatic cases in mainland China in the past week to 1,151.

The surge has been driven mostly by an outbreak in the northwestern industrial and tech hub of Xian, a city of 13 million.

The deepening outbreak in Xian will likely firm authorities' resolve to curb transmissions quickly as and when cases emerge. The city, under lockdown for 10 days as of Saturday, has reported 1,451 local symptomatic cases since Dec. 9, the highest tally for any Chinese city in 2021.

While China's case count is tiny compared to many outbreaks elsewhere in the world, forestalling major flare-ups in 2022 will be important. Beijing will be hosting the Winter Olympic Games in February, and the ruling Communist Party will hold a once-every-five-years congress, expected in the fall, where President Xi Jinping will likely secure a third term as party secretary.

The emergence of the highly transmissible Omicron variant will also drive Beijing to stick to its high vigilance against the virus. China has reported a handful of imported Omicron cases and at least one locally transmitted case.

Since August, China has tried to get any outbreak under control within about two weeks, much shorter than the four to six weeks in earlier battles against sporadic flare-ups following the initial nationwide epidemic, according to the National Health Commission.

Cities along China's borders are at higher virus risk, either due to the presence of overland transport links or entry of infected travellers from other countries. Some were hit by Delta outbreaks that resulted in harsh travel curbs last year.

Yunnan, which shares a border with Myanmar, Laos and Vietnam, reported new local symptomatic cases on 92 out of 365 days last year, or 25% of the time, more often than any other province, autonomous region or municipality.

(Graphic: Number of
days in 2021 mainland China reported new local COVID cases with symptoms,

XIAN LOCKDOWN

The Xian outbreak, which led to cases in other cities including Beijing, could be traced back to a flight arriving from Pakistan, but it was unclear how it spread to local communities.

Many people have been forbidden from leaving their residential compounds, but a city government official said on Friday curbs would be loosened in less risky compounds when the time was right.

Postgraduate student Li Jiaxin, 23, said nobody can leave the campus of her university. She spent New Year's Eve with her three room mates and was unable to meet with her boyfriend and family.

"I may be what you would consider a person with a strong sense of ritual, so I still feel a little sad that we are not together at this time," she said.

Graphic: Major China COVID-19 outbreaks in 2021,

ECONOMIC WOES

China's tough epidemic policies have helped stop its sprawling industrial sector from sliding into prolonged shutdowns, reaping important export gains as other pillars of growth weakened.

But unpredictable disruptions have shaken consumer sentiment and hammered the catering, hospitality and tourism sectors.

An employee surnamed Wang at a traditional teahouse in Kunming, the capital of Yunnan, said her company's revenues had been halved compared with pre-pandemic levels.

"Many guests from other provinces had came to our teahouse specially for a taste of Yunnan's pu'er tea, but now there are fewer of them," Wang said.

"My salary hasn't been cut, but I feel I may lose my job at any time."

Graphic: Local COVID-19 cases in mainland China in 2021,

https://www.marketscreener.com/news/latest/China-ends-2021-with-worst-COVID-week-since-taming-original-epidemic--37448601/

United, Spirit offer higher pay to on board staff during January

 United Airlines and Spirit Airlines Inc are bumping up pay for on board staff as they scramble to keep schedules intact after U.S. airlines were hammered by a week of mass cancellations.

While Spirit's flight attendants are receiving double pay on any work through Jan. 4, according to their union, United is offering triple time for pilots who pick up extra trips during January, according to an internal memo seen by Reuters.

The holiday season has been marred by delayed or canceled flights, causing chaos at most U.S. airports as sick staff and fear of contracting COVID-19 grow. Coupled with the prospect of dealing with unruly passengers, many pilots and cabin crew are even forgoing overtime incentives.

That hesitancy, combined with bad weather and tight staffing, has led to over 8,000 flight cancellations over the past eight days, according to flight-tracking website FlightAware.com.

"All flight attendants, regardless of how you have obtained your pairing, will be receiving 200% pay for any pairing that touches Dec. 28 through Jan. 4," the Association of Flight Attendants-CWA said in a statement. The union represents about 4,000 flight attendants at Spirit Airlines, according to the carrier's latest annual filing.

Earlier this year, Florida-based Spirit Airlines was forced to cancel nearly 3,000 flights due to bad weather and staffing shortages.

JetBlue Airways Corp said in a customer note on Thursday that 75% of its crew is based in the U.S. Northeast, a region that has been hit hard by COVID-19 infections. The carrier has already cut https://www.reuters.com/business/aerospace-defense/jetblue-cuts-about-1280-flights-through-mid-january-omicron-hurdles-2021-12-30/#:~:text=Dec%2030%20%20-%20JetBlue,airline%20told%20Reuters%20on%20Thursday its schedule through Jan. 13 by about 1,280 flights.

Alaska Air Group Inc said while the pandemic had hit its operations, the vast majority of cancellations and delays were due to bad weather.

The airline last week agreed to offer some benefits such as instituting pay protections in case of any reassignments on Christmas Eve, Christmas Day, and New Year's Day, the AFA said.

Hawaiian Airlines said it had not offered new incentives to its crew for working during the holiday period.

SkyWest Airlines said its operations continued to be hit due to weather and the Omicron variant, which is spreading rapidly and causing record-breaking cases across the United States.

CNBC first reported United's pay plans.

https://www.marketscreener.com/quote/stock/UNITED-AIRLINES-HOLDINGS-45899617/news/United-Spirit-offer-higher-pay-to-on-board-staff-during-January-37447552/

Big Nurses Group Opposes CDC’s Shorter Covid Isolation Guidelines

 The American Nurses Association said it opposes new guidance from the Centers for Disease Control and Prevention that “shortens the time for isolation and quarantine for health care workers infected with or exposed to Covid-19.” 

In the CDC’s new guidance, asymptomatic patients only need to isolate for five days rather than 10. These asymptomatic individuals do, however, need to continue wearing a mask for another five days when around others.

But the ANA, which says it represents more than 4 million registered nurses, on Wednesday said the CDC “ is premature and tips toward economic needs as opposed to the health of nurses.” Though the Omicron variant is spreading in the U.S., the ANA says not enough is known about its impact.

The nurses association said it is concerned such “return-to-work guidance for all health care personnel under the updated mitigation strategies will endanger the health and safety of health care workers and those they encounter.”

“While staffing shortages are challenging for facilities experiencing a surge in cases, we must prioritize health care workers’ and patients’ health and safety, including allowing for sufficient time off for health care employees,”  ANA President Ernest J. Grant said. “I urge the CDC to reconsider these guidelines and for policymakers to aggressively pursue other strategies to bolster the health care system. We support the (Biden) administration’s steps to call up more surge teams and use the Defense Production Act to increase access to testing while continuing to use every strategy to increase the number of Americans who are fully vaccinated and boosted.”

The CDC, which issued the new guidance earlier this week, said the change is “motivated by science demonstrating that the majority of SARS-CoV-2 transmission occurs early in the course of illness, generally in the 1-2 days prior to onset of symptoms and the 2-3 days after.”

CDC Director Dr. Rochelle Walensky said the updated guidance ensure people can “safely continue their daily lives.”

“The Omicron variant is spreading quickly and has the potential to impact all facets of our society,” Walensky said earlier this week.

“CDC’s updated recommendations for isolation and quarantine balance what we know about the spread of the virus and the protection provided by vaccination and booster doses,” she added. “These updates ensure people can safely continue their daily lives. Prevention is our best option: get vaccinated, get boosted, wear a mask in public indoor settings in areas of substantial and high community transmission, and take a test before you gather.”

https://www.forbes.com/sites/brucejapsen/2021/12/29/big-nurses-group-opposes-cdcs-new-covid-isolation-guidelines/

NYC allows pot smokers to light up at quarantine hotels

 New York City’s COVID-19 quarantine hotels are dope.

Anyone staying — at taxpayer expense — at one of the city’s quarantine hotels is welcome to bring their weed, which an on-staff nurse will bag, weigh and distribute for sanctioned smoke breaks. Cigarettes are also allowed.

The lodging is meant to give New Yorkers a place to recuperate from the coronavirus without sickening family or roommates or to stay safe from infection. The city started the program at the start of the pandemic in 2020 to help stop the spread of the virus by keeping people apart.

When The Post visited the LaGuardia Plaza Hotel in East Elmhurst Thursday, one of the guests was just outside the hotel entrance puffing on a bong as staff kept an eye on him from inside the lobby.

Jonathan Martin, 21, who held the orange, traffic cone-shaped bong, said he was asked if he had any pot when he arrived at the hotel on Christmas Day. He said staff put his stash in a plastic bag and took it from him, handing it back to smoke during three designated 15-minute outdoor breaks in the day.

“They allow you to bring marijuana to quarantine with you, but they don’t let you bring alcohol,” said Martin, 21, a coffee shop manager who is from Astoria and at the hotel so as not to infect his roommates.

The city is paying to put people infected with COVID-19 up in the LaGuardia Plaza Hotel.

J.C.Rice

He said a staffer scrutinized his bottle of pomegranate juice to make sure it was sealed and didn’t contain booze.

Martin said he was grateful he could still smoke.

“It’s nice to relax when I’m stuck in a room … by myself for five days,” he said.

The East Elmhurst hotel is run by the city’s Test & Trace Corps, which is part of the public Health + Hospitals system. The city could not immediately provide the cost of the program.

The city once considered serving drinks to guests who were alcoholics so they would not reject the free housing.

An insider said about 65 percent of the 420 or so guests at the hotel, and at a nearby Holiday Inn, were pot smokers.

The source said nurses had to weigh the pot after some guests claimed their weed was stolen from the holding area, which is monitored by nurses and site directors. The nurses also have to accompany smokers outside on breaks.

“I think it’s a shame. Nurses go into the field to care for patients, this is not care. Rather than offer patients help for addictions, it’s being supported,” the insider said. “Nurses are told it’s part of the job when they attempt to refuse to accompany patients to smoke marijuana or cigarettes.”

“It’s nice to relax when I’m stuck in a room … by myself for five days,” Martin said.

J.C.Rice

There were 732 calls to 911 for the LaGuardia Plaza from Jan. 1 through Thursday including 694 for an ambulance; 14 for disputes; and 10 for larcenies.

The city offers the free accommodations at the hotels for up to 10 days and also provides transportation in car services or taxis to get there and three meals a day.

Nurses at the hotel check the temperatures and oxygen saturation levels of guests during the day.

One recent LaGuardia Plaza guest said the city gave her food that contained gluten, that she couldn’t eat, and sent her home in a car with another recovering COVID-19 patient who refused to wear his mask properly and still seemed to have symptoms, according to a copy of a complaint she wrote which was obtained by The Post.

The woman said she did not leave her room for fresh air breaks during her stay because the elevators were always crowded with other patients.

“It really felt more like Corona jail than a healthcare facility,” she wrote.

A spokesman for the Test & Trace Corps. would not address the woman’s complaints or the marijuana use other than to say that clinical assessments were done for guests to determine what support they needed.

“We are proud that our hotels have provided a safe place to isolate or quarantine for nearly 30,000 New Yorkers to date, and will continue to offer this critical tool for as long as the pandemic continues,” said spokesman Adam Shrier.

https://nypost.com/2022/01/01/nyc-allows-pot-smokers-to-light-up-at-quarantine-hotels/

NYC admits prioritizing race in distributing COVID tests: leaked emails

 New York City health officials have been using race to help decide how to allocate precious coronavirus testing resources, leaked emails from the agency show.

In a conversation with reps for the Department of Health and Mental Hygiene, City Councilman Joe Borelli’s office said constituents on Staten Island’s South Shore were having trouble getting tested at city facilities.

“Our office has been receiving calls regarding the mobile NYC H+H testing sites such as Wolfes Pond Park. It appears many are waiting with delays, and are being turned away after waiting for hours,” wrote Borelli staffer Briana Nasti in a Dec. 22 email.

The agency responded the same day and informed Nasti that they would prioritize neighborhoods flagged by the city’s Taskforce on Racial Inclusion & Equity.

The task force, created by the de Blasio administration in 2020, identified 31 underserved neighborhoods to receive “priority” attention from the city.

The task force said nabes were picked based a DOHMH’s analysis of “health status, living conditions, social inequities, occupation, and COVID-19 Wave 1 impact” — though the methodology has never been released.

People scramble for free COVID-19 tests on Dec. 24.

Lev Radin/Sipa USA

Staten Island’s mostly white, middle-class South Shore — despite one of the highest COVID rates in the city during December — is not one of the priority neighborhoods. The borough has 13 city testing sites, all on the more diverse North Shore.

“I think we are clearly not on their racial and ethnic rubric priority list,” Borelli told The Post. “There was no problem pointing fingers at the South Shore of Staten Island when it came to sending enforcement goons.”

He was referring to small business owners on the island who say they have been victimized by strict enforcement of mask mandates and vax-card rules.

Queens Councilman Robert Holden said his district is still without a city testing site weeks into the Omicron surge.

New Yorkers line up for free COVID-19 tests.

Lev Radin/Sipa USA

“COVID-19 does not discriminate by politics and neither should lame duck de Blasio. We need testing sites and home test kits immediately,” Holden said. “Bill de Blasio sees districts of middle-class taxpayers who didn’t vote for him as people who don’t deserve protection from COVID-19. His administration only enters districts like ours to fine small businesses and use them as cash machines.”

A few blocks of his district lie within Woodhaven, a task-force-selected neighborhood.

A Health Department rep claimed that minority communities had “borne the brunt of this pandemic due to structural racism,” and that the tests were being distributed through community-based organizations in the selected neighborhoods.

A recent “Request for Proposals” from the DOHMH touted the agency’s commitment to racial equity.

The city is currently operating over 160 coronavirus testing sites with more 100 mobile teams and more than 60 locations.

Lev Radin/Sipa USA

“”The … DOHMH is committed to improving health outcomes for all New Yorkers by explicitly advancing racial equity and social justice. Racial equity does not mean simply treating everyone equally, but rather, allocating resources and services in such a way that explicitly addresses barriers imposed by structural racism (i.e. policies and institutional practices that perpetuate racial inequity) and White privilege,” it read.

The city is currently operating over 160 coronavirus testing sites with more 100 mobile teams and more than 60 brick and mortar locations, said Adam Shrier, an NYC Health & Hospitals rep.

The racial-equity task force didn’t immediately return requests for comment.

https://nypost.com/2022/01/01/nyc-admits-to-prioritizing-race-in-distributing-covid-tests/