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Reasons for Gratitude Amid the COVID-19 Pandemic

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Thanksgiving Tribute
Credit: Getty Images

For many of us, Thanksgiving will feel really different this year. Less will need to be more, as we celebrate alone or with our immediate household members to stay safe and help combat the surge in COVID-19 cases across most of the land. And yet, times of trouble can also help us to focus on what’s really important in our lives. So, even as we face these challenges and the range of emotions that arise with them, it’s worth remembering that this Thanksgiving, there remain many reasons to be grateful.

I’m certainly grateful for a loving family and friends that provide depth and meaning to life, even though most of us can’t be physically together and hug each other right now. My faith is also a source of comfort and reassurance at this time. I also feel a deep sense of gratitude for everyone who has sacrificed for the common good over the last several months, especially those who’ve masked up and physically distanced to provide essential services in our communities to keep everything going. You will no doubt have your own list of heroes, but here are just a few of mine:

Healthcare workers, thanks for all you do under such difficult and dangerous conditions.
Essential workers, thanks for clocking in every day. That includes bus drivers, grocery store cashiers, waste collectors, tradespeople, firefighters, law enforcement officers, and all those who deliver packages to my door.
Teachers, working remotely or in person. Thanks for your commitment to our students and continuing to bring out the best in them.
Parents, including so many now working with kids at home. Thanks for juggling responsibilities and making everything work.
Clinical trials participants. Your participation is critical for developing treatments and vaccines. Thanks to you all, including the fine examples of many public figures, including the trial participation of Senator Rob Portman and financial contribution of legendary performer Dolly Parton.
Everyone following the 3 W’s: Wear a mask, Watch your distance, and Wash your hands. Thank you for doing your part every day to keep yourself, your loved ones, and your community safe. You are our front lines in the battle.
Researchers, from both the public and private sectors, who are working in partnership all around the world. Our shared goal is to learn all we can about COVID-19 and to develop better tests, new treatments, and safe and effective vaccines.

On that note, you may have heard about the very promising interim clinical trial results of an investigational COVID-19 vaccine known as mRNA-1273, co-developed by the biotechnology company Moderna, Cambridge, MA, and NIH’s National Institute of Allergy and Infectious Diseases. That mRNA vaccine was found to be 94.5 percent effective in preventing symptomatic COVID-19. Another mRNA vaccine, developed by Pfizer and BioNTech, also recently was shown to be 95 percent effective and has now submitted an application for emergency use authorization (EUA) to the Food and Drug Administration (FDA). In addition, AstraZeneca announced that, in a late-stage clinical trial, the vaccine it developed in partnership with the University of Oxford reduced the risk of COVID-19 infection by an average of 70 percent, with up to 90 percent efficacy in one dosing regimen.

Other promising vaccine candidates continue to work their way through clinical trials, and we’ll no doubt be hearing more about those soon. It is truly remarkable to accomplish in 10 months what normally takes about 8 years. Therapeutic progress is also moving forward rapidly, with a second monoclonal antibody treatment for high-risk outpatients receiving emergency use authorization from the FDA just a few days ago.

For all of these advances, I am immensely grateful. Of course, it will take time and continued study to get a COVID-19 vaccine fully approved and distributed to all those who need it. The success of any vaccine also will hinge on people across the country—including you and all those whom I’ve recognized here—making the choice to protect themselves and others by getting vaccinated against COVID-19.

As we look ahead to that day when the COVID-19 pandemic is under control, I encourage you to take some time to jot down your own list of reasons to be grateful. Encourage family members to do the same and take some time to share them with one another, whether it’s around the table or by email, phone, or videoconferencing. The holidays are a time for making memories and—as different as it may look—this year is no different. So, while you’re enjoying your Thanksgiving meal around a smaller table, remember that you’re doing it from a place of love and gratitude. I wish for you a safe and happy Thanksgiving.

Links:

Coronavirus (COVID) (NIH)

Your Health: Holiday Celebrations and Small Gatherings (Centers for Disease Control and Prevention, Atlanta)

Your Health: Personal and Social Activities (CDC)


Mini-Lungs in a Lab Dish Mimic Early COVID-19 Infection

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Credit: Arvind Konkimalla, Tata Lab, Duke University, Durham, NC

Researchers have become skilled at growing an array of miniature human organs in the lab. Such lab-grown “organoids” have been put to work to better understand diabetes, fatty liver disease, color vision, and much more. Now, NIH-funded researchers have applied this remarkable lab tool to produce mini-lungs to study SARS-CoV-2, the coronavirus that causes COVID-19.

The intriguing bubble-like structures (red/clear) in the mini-lung pictured above represent developing alveoli, the tiny air sacs in our lungs, where COVID-19 infections often begin. In this organoid, the air sacs consist of many thousands of cells, all of which arose from a single adult stem cell isolated from tissues found deep within healthy human lungs. When carefully nurtured in lab dishes, those so-called alveolar epithelial type-2 cells (AT2s) begin to multiply. As they grow, they spontaneously assemble into structures that closely resemble alveoli.

A team led by Purushothama Rao Tata, Duke University School of Medicine, Durham, NC, developed these mini-lungs in a quest to understand how adult stem cells help to regenerate damaged tissue in the deepest recesses of the lungs, where SARS-CoV-2 attacks. In earlier studies, the researchers had shown it was possible for these cells to produce miniature alveoli. But there was a problem: the “soup” they used to nurture the growing cells included ingredients that weren’t well defined, making it hard to characterize the experiments fully.

In the study, now reported in Cell Stem Cell, the researchers found a way to simplify and define that brew. For the first time, they could produce mini-lungs consisting only of human lung cells. By growing them in large numbers in the lab, they can now learn more about SARS-CoV-2 infection and look for new ways to prevent or treat it.

Tata and his collaborators at the University of North Carolina, Chapel Hill, have already confirmed that SARS-CoV-2 infects the mini-lungs via the critical ACE2 receptor, just as the virus is known to do in the lungs of an infected person.

Interestingly, the cells also produce cytokines, inflammatory molecules that have been tied to tissue damage. The findings suggest the cytokine signals may come from the lungs themselves, even before immune cells arrive on the scene.

The heavily infected lung cells eventually self-destruct and die. In an unexpected turn of events, they even induce cell death in some neighboring healthy cells that are not infected. The relevance of the studies to the clinic was boosted by the finding that the gene activity patterns in the mini-lungs are a close match to those found in samples taken from six patients with severe COVID-19.

Now that he’s got the recipe down, Tata is busy making organoids and helping to model COVID-19 infections, with the hope of identifying and testing promising new treatments. It’s clear these mini-lungs are breathing some added life into the basic study of COVID-19.

Reference:

[1] Human lung stem cell-based alveolospheres provide insights into SARS-CoV-2-mediated interferon responses and pneumocyte dysfunction. Katsura H, Sontake V, Tata A, Kobayashi Y, Edwards CE, Heaton BE, Konkimalla A, Asakura T, Mikami Y, Fritch EJ, Lee PJ, Heaton NS, Boucher RC, Randell SH, Baric RS, Tata PR. Cell Stem Cell. 2020 Oct 21:S1934-5909(20)30499-9.

Links:

Coronavirus (COVID-19) (NIH)

Tata Lab (Duke University School of Medicine, Durham, NC)

NIH Support: National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences; National Institute of Diabetes and Digestive and Kidney Diseases


Discussing COVID-19 at the Washington National Cathedral

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On November 12, I took my 3D model of SARS-CoV-2 along with me to the annual Ignatius Forum at the Washington National Cathedral. Following a presentation on the COVID-19 pandemic by NIH’s Anthony Fauci, I participated in a panel discussion with infectious disease expert Luciana Borio (center). New Hampshire Superior Court Judge Amy L. Ignatius (right) moderated the video-recorded discussion. Credit: Washington National Cathedral


Can Autoimmune Antibodies Explain Blood Clots in COVID-19?

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Blood Clots
Caption: Illustration showing a blood vessel with a platelet clot (yellow). Red blood cells (red), neutrophils (purple), and Y-shaped antibodies called aPL (white) circulate through the vessel. Credit: Stephanie King/Michigan Medicine

For people with severe COVID-19, one of the most troubling complications is abnormal blood clotting that puts them at risk of having a debilitating stroke or heart attack. A new study suggests that SARS-CoV-2, the coronavirus that causes COVID-19, doesn’t act alone in causing blood clots. The virus seems to unleash mysterious antibodies that mistakenly attack the body’s own cells to cause clots.

The NIH-supported study, published in Science Translational Medicine, uncovered at least one of these autoimmune antiphospholipid (aPL) antibodies in about half of blood samples taken from 172 patients hospitalized with COVID-19. Those with higher levels of the destructive autoantibodies also had other signs of trouble. They included greater numbers of sticky, clot-promoting platelets and NETs, webs of DNA and protein that immune cells called neutrophils spew to ensnare viruses during uncontrolled infections, but which can lead to inflammation and clotting. These observations, coupled with the results of lab and mouse studies, suggest that treatments to control those autoantibodies may hold promise for preventing the cascade of events that produce clots in people with COVID-19.

Our blood vessels normally strike a balance between producing clotting and anti-clotting factors. This balance keeps us ready to seal up vessels after injury, but otherwise to keep our blood flowing at just the right consistency so that neutrophils and platelets don’t stick and form clots at the wrong time. But previous studies have suggested that SARS-CoV-2 can tip the balance toward promoting clot formation, raising questions about which factors also get activated to further drive this dangerous imbalance.

To learn more, a team of physician-scientists, led by Yogendra Kanthi, a newly recruited Lasker Scholar at NIH’s National Heart, Lung, and Blood Institute and his University of Michigan colleague Jason S. Knight, looked to various types of aPL autoantibodies. These autoantibodies are a major focus in the Knight Lab’s studies of an acquired autoimmune clotting condition called antiphospholipid syndrome. In people with this syndrome, aPL autoantibodies attack phospholipids on the surface of cells including those that line blood vessels, leading to increased clotting. This syndrome is more common in people with other autoimmune or rheumatic conditions, such as lupus.

It’s also known that viral infections, including COVID-19, produce a transient increase in aPL antibodies. The researchers wondered whether those usually short-lived aPL antibodies in COVID-19 could trigger a condition similar to antiphospholipid syndrome.

The researchers showed that’s exactly the case. In lab studies, neutrophils from healthy people released twice as many NETs when cultured with autoantibodies from patients with COVID-19. That’s remarkably similar to what had been seen previously in such studies of the autoantibodies from patients with established antiphospholipid syndrome. Importantly, their studies in the lab further suggest that the drug dipyridamole, used for decades to prevent blood clots, may help to block that antibody-triggered release of NETs in COVID-19.

The researchers also used mouse models to confirm that autoantibodies from patients with COVID-19 actually led to blood clots. Again, those findings closely mirror what happens in mouse studies testing the effects of antibodies from patients with the most severe forms of antiphospholipid syndrome.

While more study is needed, the findings suggest that treatments directed at autoantibodies to limit the formation of NETs might improve outcomes for people severely ill with COVID-19. The researchers note that further study is needed to determine what triggers autoantibodies in the first place and how long they last in those who’ve recovered from COVID-19.

The researchers have already begun enrolling patients into a modest scale clinical trial to test the anti-clotting drug dipyridamole in patients who are hospitalized with COVID-19, to find out if it can protect against dangerous blood clots. These observations may also influence the design of the ACTIV-4 trial, which is testing various antithrombotic agents in outpatients, inpatients, and convalescent patients. Kanthi and Knight suggest it may also prove useful to test infected patients for aPL antibodies to help identify and improve treatment for those who may be at especially high risk for developing clots. The hope is this line of inquiry ultimately will lead to new approaches for avoiding this very troubling complication in patients with severe COVID-19.

Reference:

[1] Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Zuo Y, Estes SK, Ali RA, Gandhi AA, Yalavarthi S, Shi H, Sule G, Gockman K, Madison JA, Zuo M, Yadav V, Wang J, Woodard W, Lezak SP, Lugogo NL, Smith SA, Morrissey JH, Kanthi Y, Knight JS. Sci Transl Med. 2020 Nov 2:eabd3876.

Links:

Coronavirus (COVID-19) (NIH)

Antiphospholipid Antibody Syndrome (National Heart Lung and Blood Institute/NIH)

Kanthi Lab (National Heart, Lung, and Blood Institute, Bethesda, MD)

Knight Lab (University of Michigan)

ACTIV (NIH)

NIH Support: National Heart, Lung, and Blood Institute


Planning Your Holidays During the COVID-19 Pandemic

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Thanksgiving 2020
Credit: Getty Images

With the holiday season fast approaching and coronavirus disease 2019 (COVID-19) surging in most parts of the country, millions of Americans—including me and my family—will break with tradition this year to celebrate in ways that we hope will help to keep us all safe and healthy. Granted, this may present some difficult emotional and logistical challenges, but I’m confident that the American can-do spirit will rise to meet those challenges.

I also recognize that this will be hard for many of us. Celebrating holidays alone or with your immediate household members can sound rather dreary. After all, who wants to roast and carve a turkey for just a few people? But, if you look at it another way, the pandemic does offer opportunities to make this holiday a season to remember in new and different ways. Here are a couple of ideas that you may want to consider:

Send Gifts. Although COVID-19 has changed our lives in many ways, sending cards or gifts remains a relatively easy way to let loved ones know that you’re thinking of them. Who wouldn’t want to receive some home-baked goodies, a basket of fresh fruit, or a festive wreath? If you enjoy knitting, candle making, or other ways of crafting gifts for the holidays, now’s the time to start planning for Thanksgiving through the New Year.

Make Videos. When I’m visiting family, there is often music involved—with guitar, piano, and maybe some singing. But, this year, I’ll have to be content with video recording a few songs and sending them to others by text or email. Come to think of it, the kids and the grandkids might enjoy these songs just as much—or even more—if they can watch them at a time and place that works best for them. (On the other hand, some of them might roll their eyes and decide not to open that video file!) If you don’t play a guitar or like to sing, you can still make your own holiday-themed videos. Maybe share a dance routine, a demonstration of athletic skill, or even some stand-up comedy. The key is to have fun and let your imagination run free.

Share a Meal Remotely. Most of our end-of-the-year holidays involve the family sitting around a table overflowing with delicious food. With all of the videoconferencing platforms now available, it is easy to set aside a block of time to share a meal and good conversation remotely with friends and family members, whether they live nearby or across the country. Rather than one cook slaving over a hot stove or a certain person monopolizing the dinner table conversation, everyone gets a chance to cook and share their stories via their smartphone, tablet, or laptop. You can compare your culinary creations, swap recipes, and try to remember to leave room for dessert. If you have a tradition of playing games or giving thanks for your many blessings, you can still do many of these activities remotely.

Take an After-Dinner Walk. Due to the physical demands and psychological impacts of the COVID-19 pandemic, it’s been difficult for many of us to stay physically active. The key is making exercise a daily priority, and the holidays are no different. After your holiday meal, go on a virtual group walk through your respective neighborhoods to work off the food. Thanks to your smartphone’s camera, you can share your time outdoors and all of the interesting sights along the way. (Yes, the new playground in the local park looks fantastic, and the neighbors really did just paint their house purple!)

Stay Safe. If you plan to go ahead and join a holiday gathering in person, it’s important to remain vigilant, even when interacting with dear friends and loved ones. The greatest risk for spread of COVID-19 right now is these family gatherings. Remember there are risks associated with travel and with interacting with people who’ve not been tested for the coronavirus prior to the event, especially if they reside in a COVID hot spot—which is almost everywhere these days. Try to keep any family gatherings brief and relatively small, about five people or less. If the weather permits, hold the get-together outdoors.

To protect yourself and your loved ones, both now and over the holidays, please follow these 3 W’s:

Wear a mask when you are out in public and when you are indoors with people who are not part of your immediate household. The only exception is while eating or drinking!
Watch your distance, staying at least 6 feet away from people who are not part of your immediate household.
Wash your hands thoroughly and frequently.

Making all of these adjustments is a lot to consider when you’re trying to have a good time and there are children and older adults in the mix. That’s why I and my wife Diane decided the best plan for us this holiday season is to stay home in Maryland and forgo our traditional trips to family in Michigan and North Carolina. Not only did we want to reduce the risk of possibly contracting COVID-19 from—or transmitting it to—our faraway loved ones, we want to do everything we can to protect our local friends and co-workers from the coronavirus.

While this holiday season is likely to be memorable in ways that we never could have imagined, I’m confident that, thanks to the rapid advances being made by medical research, we ultimately will get the COVID-19 pandemic under control so we can once again give everyone we love a big hug in person. Until then, please stay safe. Wishing each of you a wonderful and healthful holiday season, starting with a Happy Thanksgiving!

Links:

Coronavirus (COVID) (NIH)

Your Health: Holiday Celebrations and Small Gatherings (Centers for Disease Control and Prevention, Atlanta)

Your Health: Personal and Social Activities (CDC)


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