Photographer Captures 'Last Stop' in Britain's Covid War

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutNew Variants TrackerAdvertisementContinue reading the main storySupported byContinue reading the main storyTimes Insider‘This Is the Last Stop’: Shooting Britain’s Struggle Against CovidAfter receiving access to hospitals, nursing homes and burial sites, I saw up close the nation’s agony, and grit.Health care workers in the intensive care unit at the Homerton hospital in London turn a patient onto her back to help her breathe.Credit…Andrew Testa for The New York TimesMarch 2, 2021, 5:00 a.m. ETTimes Insider explains who we are and what we do, and delivers behind-the-scenes insights into how our journalism comes together.I had covered wars before, in the Balkans and Afghanistan. They were shooting wars where journalists — often foolishly — convinced themselves that they had a chance of identifying and sidestepping danger.But in Britain’s war against Covid-19, the days I spent as a freelance photojournalist covering the intensive care unit of the Homerton hospital in East London involved danger with every breath. The project for The New York Times documenting the nation’s fight against the coronavirus was terrifying and awe-inspiring. Terrifying because of potential exposure to an invisible killer that has claimed over 120,000 lives in Britain and more than 2.5 million globally. Awe-inspiring because I could witness the remarkable courage, professionalism and sheer grit of medical personnel whose daily routines placed them on the very cusp of life and death.Even the most advanced modern medicine offers no magic cures. For those who can’t make it out of the I.C.U., there is only death. This is the last stop. What stayed with me afterward was the fear in people’s eyes as they joined what could be the final battle. For the medical staff, the burden of responsibility is enormous.As Britain approaches a gradual loosening of its most draconian lockdown, and with millions of people securing access to vaccines, images of this terminal conflict do not fit easily into the official narrative.A vaccination center inside the Cathedral in Salisbury. Credit…Andrew Testa for The New York TimesMany Britons are probably unaware of the brutal reality of the I.C.U.: the constant bleeps of monitors everywhere; the staff hurrying to flip over, or “prone,” patients to help them breathe; the all-too-brief respites that give way to frenetic activity.Raising this awareness took months. My editors — Gaia Tripoli in London and David Furst in New York — and the researcher Amy Woodyatt and I called hospitals, mortuaries, crematories, funeral parlors and ambulance depots seeking access to chronicle this moment in the pandemic, only to be turned down. Often, we were told that photography was incompatible with the dignity of the dead.Finally, some were willing to cooperate, and after I was able to observe their toil, we began to assemble a portfolio to tell the story of Britain’s struggle. We wanted our images to reflect more than one area of London or one ethnic group. The list of subjects grew from a care home in Scarborough on the northeastern coast, to a funeral director in the English Midlands, to those dealing with Islamic and other rites in the capital.Prayers before a burial of a Muslim victim. One aim of the project was to avoid representing just one ethnic group in Britain that has been affected. Credit…Andrew Testa for The New York TimesWith this assignment came a new and unfamiliar set of ground rules and procedures designed to protect not only me but also those around me — both at work and at home..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-c7gg1r{font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:0.875rem;line-height:0.875rem;margin-bottom:15px;color:#121212 !important;}@media (min-width:740px){.css-c7gg1r{font-size:0.9375rem;line-height:0.9375rem;}}.css-1sjr751{-webkit-text-decoration:none;text-decoration:none;}.css-1sjr751 a:hover{border-bottom:1px solid #dcdcdc;}.css-rqynmc{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.9375rem;line-height:1.25rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-rqynmc{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-rqynmc strong{font-weight:600;}.css-rqynmc em{font-style:italic;}.css-yoay6m{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}@media (min-width:740px){.css-yoay6m{font-size:1.25rem;line-height:1.4375rem;}}.css-1dg6kl4{margin-top:5px;margin-bottom:15px;}.css-16ed7iq{width:100%;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:center;-webkit-justify-content:center;-ms-flex-pack:center;justify-content:center;padding:10px 0;background-color:white;}.css-pmm6ed{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}.css-pmm6ed > :not(:first-child){margin-left:5px;}.css-5gimkt{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.8125rem;font-weight:700;-webkit-letter-spacing:0.03em;-moz-letter-spacing:0.03em;-ms-letter-spacing:0.03em;letter-spacing:0.03em;text-transform:uppercase;color:#333;}.css-5gimkt:after{content:’Collapse’;}.css-rdoyk0{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;-webkit-transform:rotate(180deg);-ms-transform:rotate(180deg);transform:rotate(180deg);}.css-eb027h{max-height:5000px;-webkit-transition:max-height 0.5s ease;transition:max-height 0.5s ease;}.css-6mllg9{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;position:relative;opacity:0;}.css-6mllg9:before{content:”;background-image:linear-gradient(180deg,transparent,#ffffff);background-image:-webkit-linear-gradient(270deg,rgba(255,255,255,0),#ffffff);height:80px;width:100%;position:absolute;bottom:0px;pointer-events:none;}#masthead-bar-one{display:none;}#masthead-bar-one{display:none;}.css-1pd7fgo{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-1pd7fgo{padding:20px;width:100%;}}.css-1pd7fgo:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1pd7fgo{border:none;padding:20px 0 0;border-top:1px solid #121212;}.css-1pd7fgo[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-1pd7fgo[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-1pd7fgo[data-truncated] .css-5gimkt:after{content:’See more’;}.css-1pd7fgo[data-truncated] .css-6mllg9{opacity:1;}.css-k9atqk{margin:0 auto;overflow:hidden;}.css-k9atqk strong{font-weight:700;}.css-k9atqk em{font-style:italic;}.css-k9atqk a{color:#326891;-webkit-text-decoration:none;text-decoration:none;border-bottom:1px solid #ccd9e3;}.css-k9atqk a:visited{color:#333;-webkit-text-decoration:none;text-decoration:none;border-bottom:1px solid #ddd;}.css-k9atqk a:hover{border-bottom:none;}Covid-19 Vaccines ›What You Need to Know About the Vaccine RolloutProviders in the U.S. are administering about 1.3 million doses of Covid-19 vaccines per day, on average. Almost 30 million people have received at least one dose, and about 7 million have been fully vaccinated. How many people have been vaccinated in your state?The U.S. is far behind several other countries in getting its population vaccinated.In the near future, travel may require digital documentation showing that passengers have been vaccinated or tested for the coronavirus.When can you get the vaccine? What are the vaccine’s side effects? Is it safe to take during pregnancy? We’ve have answers to many of your questions. In the Homerton I.C.U., they called it “donning and doffing” of personal protective equipment. I switched my day clothes for scrubs and a surgical gown; a close-sealing mask and goggles; overshoes; and a hair covering. I pared down my equipment to two cameras. And at the end of the day’s shooting, I followed a very strict protocol developed by the I.C.U. staff for removing protective gear.Once home, I laundered all my clothes, showered, cleaned equipment with anti-viral wipes and exposed it to a UVC light sanitizer. I was not eligible to be vaccinated, but I had a precautionary coronavirus test during the assignment that came up negative.The I.C.U. in the Homerton hospital. Shooting in the unit required following a strict set of safety rules. Credit…Andrew Testa for The New York TimesUltimately, I told myself, I just had to trust my equipment. But there is always gnawing doubt. The coronavirus frightens you twice over: first by its ability to infect you personally, and second by the overwhelming fear that you might inadvertently pass it on to your family.There is never any question about its power. On my second day in the Homerton I.C.U., two people died within 25 minutes of each other. Usually, the medical authorities try to provide access for family members to say goodbye. But with patients in induced comas and beyond hope, it is a cruelly one-sided exchange of farewells.And yet the counter-imagery of dedication is always there, too, just as evident in these images as the losses. As one survivor remarked, the medical teams always go the extra mile. “They are blessed,” he said.AdvertisementContinue reading the main story

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Here is What We Know About the Rollout of the Johnson & Johnson Vaccine.

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutNew Variants TrackerAdvertisementContinue reading the main storyCovid-19: The U.S. Is Edging Toward Normal, Alarming Some OfficialsHere is what we know about the rollout of the Johnson & Johnson vaccine.March 1, 2021, 5:00 p.m. ETMarch 1, 2021, 5:00 p.m. ETJohnson & Johnson said it would start shipping millions of doses early this week after the Food and Drug Administration granted emergency use authorization for its vaccine on Saturday.CreditCredit…Pool photo by Timothy D. EasleyWhen Johnson & Johnson’s coronavirus vaccine won emergency use authorization on Saturday from the Food and Drug Administration, the move augmented the nation’s vaccination effort with a third major tool — one that differs markedly from the first two authorized vaccines, made by Pfizer-BioNTech and Moderna.Most notably, it is administered in a single dose instead of two, and can be kept unfrozen in an ordinary refrigerator for up to three months — features that promise greater flexibility as public health officials try to immunize Americans as quickly as possible.Much is still to be determined about how this new tool will be used. Here is what we know so far.When will people start getting the new vaccine?Within the next few days. Johnson & Johnson started shipping out doses on Monday, and they can be used as soon as they reach vaccination sites starting on Tuesday.Will adding the new supply speed up vaccination efforts?At first, the increase in availability will be limited. The company had about 3.9 million doses on hand to ship right away, but after that, deliveries could be patchy for a few weeks. (For comparison, the nation is using up that many doses of the Pfizer-BioNTech and Moderna vaccines in a little more than two days.)By the end of March, Johnson & Johnson says it will ship roughly 16 million more doses. Even so, the Pfizer-BioNTech and Moderna vaccines will continue to make up the majority of the nation’s supply.How is the new vaccine being allocated?The same way the two earlier vaccines are: in proportion to each state or territory’s population.Who will get the new vaccine?That’s still under discussion. The Centers for Disease Control and Prevention has said that the vaccine can be given to people 18 and over, and state officials are working out what their policies will be.Because the new vaccine is given in a single shot and doesn’t require cold storage, some experts and officials have suggested directing it toward hard-to-reach segments of the population (like rural residents or homeless people), or to people who might not keep an appointment for a second shot (like college students or those with mobility issues).But there is concern about appearing to favor or disfavor some groups, and the Biden administration has said it will insist that the new vaccine be distributed equitably.Will I be able to choose which vaccine I receive?That’s not clear. Right now, people are getting whichever vaccine the site has on hand when their turn comes, and appointment scheduling systems generally don’t tell users beforehand which it will be. Depending on how states decide to deploy the Johnson & Johnson vaccine, though, it may be possible to effectively choose what you get by choosing where you sign up to get it.Which vaccine should I prefer?Health experts say the best shot is the one you can get the soonest, whichever one it turns out to be. All three authorized vaccines are highly protective, and the differences among them pale in comparison, they say, with the risk you would run by being picky and passing up a chance to get a shot because it was not your top choice.How the Johnson & Johnson Vaccine WorksAn adenovirus helps prime the immune system to fight the coronavirus.AdvertisementContinue reading the main story

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How Johnson & Johnson's Vaccine Differs From Pfizer and Moderna's

AdvertisementContinue reading the main storyCovid-19: The U.S. Is Edging Toward Normal, Alarming Some OfficialsHere is how Johnson & Johnson’s vaccine differs from Pfizer’s and Moderna’s.Feb. 28, 2021, 2:21 p.m. ETFeb. 28, 2021, 2:21 p.m. ETThe vaccines already in wide use in the United States are given in two doses several weeks apart, while the newly authorized Johnson & Johnson vaccine is given in a single dose.Credit…Pool photo by Timothy D EasleyLeer en españolA third effective weapon was added to America’s arsenal against the coronavirus on Saturday when the Food and Drug Administration granted emergency use authorization for a vaccine developed by Johnson & Johnson.The company said it would start shipping millions of doses early this week, and would provide the United States with 100 million doses by the end of June. Together with 600 million doses of the nation’s first two authorized vaccines, made by Pfizer-BioNTech and Moderna, that are due to be delivered over the next four months, that ought to be enough to cover every American adult who wants to be vaccinated.The new vaccine differs markedly from the two already in use in the United States. Here is how they compare.One shot instead of twoThe Johnson & Johnson vaccine is administered in a single shot, while the Pfizer-BioNTech and Moderna vaccines are given in two shots several weeks apart.The way it worksThe Johnson & Johnson vaccine uses a different method to prime the body to fight off Covid-19: a viral vector called Ad26. Viral vectors are common viruses that have been genetically altered so that they do not cause illness but can still cause the immune system to build up its defenses. The Pfizer-BioNTech and Moderna vaccines use messenger RNA to do that.How well it worksThe Johnson & Johnson vaccine is rated as highly effective at preventing serious illness and death, as the Pfizer-BioNTech and Moderna vaccines are. It is also very effective at preventing milder illness, though a bit less so than those two. It appears to do well against the highly contagious B.1.351 variant, first identified in South Africa, that has given at least one other vaccine candidate trouble.Storage and handlingThe Johnson & Johnson vaccine does not have to be stored at extremely low temperatures like the Pfizer-BioNTech vaccine. It can safely be kept in an ordinary refrigerator for three months, much longer than the Moderna vaccine, which spoils after a month if not kept frozen.Side effectsThe Johnson & Johnson vaccine appears to be less prone than the Pfizer-BioNTech and Moderna vaccines to trigger the kinds of side effects that require monitoring after the injection, which may make it more suitable for use at drive-through vaccination sites. There have been reports that side effects tend to be felt more strongly after second doses, which the Johnson & Johnson vaccine does not require.AdvertisementContinue reading the main story

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Surf’s Up. The Temperature Isn’t.

Curtis Eichenberger exits the water at Lake Huron’s Georgian Bay.The World Through a LensSurf’s Up. The Temperature Isn’t.Growing numbers of surfers are taking to the Great Lakes — even when the weather is well below freezing.Curtis Eichenberger exits the water at Lake Huron’s Georgian Bay.Credit…Supported byContinue reading the main storyMarch 1, 2021It’s a cold Friday morning in late January. The snow has been falling all night. With two friends, Curtis Eichenberger and Brian McElroy, I’m heading northwest from the town of Collingwood, Ontario, to the shores of Lake Huron in Bruce County. It’s a two-hour drive, and we’re hoping the ice has taken hold of the shoreline.We park at the end of a rural road and begin the 20-minute walk to the shore. Curtis and Brian are in wetsuits and jackets, carrying their surfboards, walking down a forest path in a heavy snowstorm.I can’t help thinking that this is a quintessentially Canadian experience.Brian McElroy and Curtis Eichenberger make their way — through a snowstorm — to the shore of Lake Huron.Brian and Curtis discuss the water before hitting the waves.Our first glance at the water has Curtis and Brian excited: The waves are head high, and the sets are consistent. There are a couple of other hardy surfers out here, but it’s better than their local spot, which recently drew a crowd of some 25 people.The drive, it seems, was worth it.Curtis, suited up to surf.Curtis pours hot water in his wetsuit boots to help warm up his feet.Brian in Lake Huron.In recent years there’s been a significant increase in the popularity of lake surfing in North America. Unlike ocean surfers, who often depend partly on tides, lake surfers rely solely on strong, sustained winds. The stormy winter months often bring the biggest waves — and therefore the best surfing conditions.Curtis in Georgian Bay, at Sunset Point Beach in Collingwood, Ontario.January water temperatures on the Great Lakes are typically between 32 and 40 degrees Fahrenheit. Without a wetsuit in such temperatures, most people lose dexterity in just a few minutes. Exhaustion or loss of consciousness would occur after 15 to 30 minutes.Curtis stretches before surfing in Georgian Bay at Delphi Point Beach.Curtis, coated in ice.Still, the Great Lakes are becoming wintertime hot spots for the ocean-starved surfers who live in the area. Desperate for waves, devotees are often glued to local surf chat groups and obsessive about wind and wave forecasts.At a moment’s notice, they’re ready to clear their schedules, drive for hours, squeeze into their 6-millimeter-thick neoprene wetsuits and don (even thicker) booties and gloves, all in hopes of catching a good swell before the waves subside — or before they lose too much body heat.Surfers wait for waves in Georgian Bay.Curtis and Brian have been friends since they were kids, growing up in a small ski town north of Toronto, on Georgian Bay. They first had a taste of ocean surfing as teenagers on separate trips to New Zealand around 2003. Since then, they’ve surfed in dreamy — and warm — beach destinations all over the world: Australia, California, Costa Rica, El Salvador, Hawaii, Mexico, Nicaragua, Portugal.After driving for two hours from Toronto, Randy Luke Enns enters Georgian Bay with his surfboard at Sunset Point Beach.A surfer’s sandals are covered in snow during a lake-surfing session in Georgian Bay.“It was out of the love for ocean surfing that I ventured out into the Great Lakes,” Brian said. “Growing up landlocked, you find a way to surf throughout the year.”Matt Wilcox, a lake surfer, takes a break from surfing at Sunset Point Beach.Stephanie Hebb off the coast of Sunset Point Beach.All around the Great Lakes region — and locally in places such as Kincardine, Port Elgin and, of course, Toronto — there are surf shops that sell expensive winter surfing gear, including wetsuits and surfboards. Some of the more passionate surfers have started shaping their own surfboards in their basements or garages.Madison Tylak and Joey Braden walk into Georgian Bay at Sunset Point Beach.Jacqueline Warll and Matt Wilcox at Sunset Point Beach.There are Great Lakes surf clubs, magazines, wave forecasting seminars and competitions. And all of this is taking place hundreds of miles from the nearest ocean, and thousands of miles from the warm-ocean surf destinations that you see in movies and magazines.Georgian Bay during a snowstorm.Surfing on the Great Lakes is nothing new; people have been doing it for many decades. But what used to be a relatively niche hobby along secluded shorelines is now in full view on social media, where interest in the sport is compounding.The coronavirus pandemic has also added to its popularity. With travel restrictions in place, and with many hockey rinks, ski hills and exercise facilities closed, people have been searching for new types of exercise and entertainment — and, in particular, activities that are independent, informal and can be done closer to home and while distanced from others.Paul Reid walks into Georgian Bay.Scott Miller leaves the water after surfing in Georgian Bay at Sunset Point Beach.After two hours, Curtis and Brian emerge from the water with freezing extremities. Icicles cling to their eyebrows.Taking shelter in the trees, on the snow-covered ground, the two friends are invigorated, excited like the teenage versions of themselves who’d just learned to surf.Jordan Ward leaves the water after surfing in Lake Huron.Ryan Carter is a photographer based near Toronto. You can follow his work on Instagram.Follow New York Times Travel on Instagram, Twitter and Facebook. And sign up for our weekly Travel Dispatch newsletter to receive expert tips on traveling smarter and inspiration for your next vacation.AdvertisementContinue reading the main story

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Why I Overcame My Vaccine Hesitancy

#masthead-section-label, #masthead-bar-one { display: none }The Coronavirus OutbreakliveLatest UpdatesMaps and CasesRisk Near YouVaccine RolloutNew Variants TrackerAdvertisementContinue reading the main storySupported byContinue reading the main storyPersonal HealthWhy I Overcame My Vaccine HesitancyThe more people who become immune to the virus, the less this scourge will be able to mutate and evade the vaccines already available.Credit…Gracia LamMarch 1, 2021Had I been polled last fall, I would have registered as a Covid vaccine skeptic. I told anyone who asked that I was going to wait at least six months after a vaccine was approved, by which time I hoped we’d know more about the degree and possibly the duration of its effectiveness and its potential side effects, especially in the elderly.I was hardly alone in my concern that political influence might result in premature approval of a vaccine before its safety was well established.Well, that hesitancy quickly dissipated after listening to reports from the directors of the Food and Drug Administration and the Centers for Disease Control and Prevention and several vaccine experts I know and trust, all of whom gave an enthusiastic thumbs-up to both the Pfizer and Moderna vaccines.So in mid-January, when Gov. Andrew M. Cuomo of New York announced that residents 75 and older would qualify for the vaccine, I found a computerized link to schedule an appointment five days later.At the mass vaccination site I went to in Brooklyn, everyone I encountered was cheerful, patient and reassuring, even the young woman checking me in who couldn’t find me on her list of 3 p.m. appointments. “Don’t worry,” she said reassuringly, “you’ll get the vaccine.”At the next window, a young man from Nigeria checked my ID and Medicare card and figured out what had happened. Turned out I had inadvertently booked a 3 a.m. appointment, not realizing the site was open 24-7. Another “don’t worry,” and I moved on to a young technician from Florida who painlessly injected the Moderna vaccine into my left arm.I then sat in a holding tent for 15 minutes to be sure I would have no serious reactions. The next day I got a text: “Hi Jane, It’s time for your daily v-safe check-in” and a link to a C.D.C. site that asked: How are you feeling today? (Good, Fair, Poor); Have you had a fever or felt feverish today? (yes, no); followed by a symptom check, first at the injection site for pain, redness, swelling or itching and then generally for chills, headache, joint pains, muscle or body aches, fatigue or tiredness, nausea, vomiting, diarrhea, abdominal pain and rash or any other symptoms I wanted to report.Finally, I was asked several overall health impact questions about my ability to work and do my normal daily activities and whether I needed to consult a health care professional. I received the same text at the same time each day for more than a week, and was also given a link if I wanted to send a report to the Vaccine Adverse Event Reporting System.The second dose, administered 34 days later, went even more smoothly. By then I’d spoken to dozens of others of various ages who had gotten both shots. Only two reported bad reactions — fever, nausea, extreme fatigue — that lasted a day or two. I was prepared for the worst, but it never happened. My arm, shoulder and neck hurt the first night, but most of the pain was gone the next morning. Although my son was on call in case I couldn’t walk my dog, his help wasn’t needed. I was even able to swim that afternoon.But I assure you, even if I’d had a bad post-vaccine reaction, I would have sucked it up as a small price to pay for protection against a most devastating and too-often deadly disease like Covid-19. And I will continue to urge everyone and anyone I meet to do their damnedest to get immunized against Covid-19, especially now that potentially more potent variants are beginning to appear and spread.The Coronavirus Outbreak

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Assessing a compound's activity, not just its structure, could accelerate drug discovery

Assessing a drug compound by its activity, not simply its structure, is a new approach that could speed the search for COVID-19 therapies and reveal more potential therapies for other diseases.
This action-based focus — called biological activity-based modeling (BABM) — forms the core of a new approach developed by National Center for Advancing Translational Sciences (NCATS) researchers and others. NCATS is part of the National Institutes of Health (NIH). Researchers used BABM to look for potential anti-SARS-CoV-2 agents whose actions, not their structures, are similar to those of compounds already shown to be effective.
NCATS scientists Ruili Huang, Ph.D., and Wei Zheng, Ph.D., led the research team that created the approach. Their findings were posted online Feb. 23 by the journal Nature Biotechnology.
“With this new method, you can find completely new chemical structures based on activity profiles and then develop completely new drugs,” Huang explained. Thus, using information about a compound’s biological activity may expand the pool of promising treatments for a wide range of diseases and conditions.
When researchers seek new compounds or look for existing drugs to repurpose against new diseases, they are increasingly using screening tools to predict which drugs might be good candidates. Virtual screening, or VS, allows scientists to use advanced computer analyses to find potentially effective candidates from among millions of compounds in collections.
Traditional VS techniques look for compounds with structures similar to those known to be effective against a particular target on a pathogen or cell, for example. Those structural similarities are then assumed to deliver similar biological activities.

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With BABM, however, researchers don’t need to know a compound’s chemical structure, according to Huang. Instead, they use a profile of a compound’s activity patterns — how it behaves at multiple concentrations against a panel of targets or tests — to predict its potential effectiveness against a new target or in a new drug assay.
The now-widespread use of quantitative high-throughput screening (qHTS) allows BABM more accuracy in its predictions. qHTS assesses a compound’s effectiveness at multiple concentrations in thousands of tests over time. That practice provides far more detail about how a compound behaves than does traditional high-throughput screening, which tests only a single concentration of the compound. The information generated by qHTS creates a stronger biological activity profile — also known as a signature — for each one of millions of compounds.
To test the BABM approach, the researchers tapped the vast pool of data generated by hundreds of qHTS analyses run on NCATS’ in-house collection of more than 500,000 compounds and drugs. First, they verified BABM’s ability to use activity profiles to identify compounds already shown to be effective against the Zika and Ebola viruses. BABM also identified new compounds that showed promise against those viruses.
The scientists then turned to SARS-CoV-2, the virus that causes COVID-19. They applied BABM, a structure-based model and a combined approach to analyze the NCATS library’s compounds to find potential anti-SARS-CoV-2 agents. BABM predicted that the activity profiles of 311 compounds might indicate promise against the coronavirus.
The researchers then had an outside laboratory test those 311 compounds against the live SARS-CoV-2 virus. The result: Nearly one-third of the BABM-backed compounds (99) showed antivirus activity in the test. The BABM-driven prediction hit rate topped that of the structure-based model — and combining the activity-based and structure-based models yielded even better predictive results.
A key advantage to BABM is speed. “This method is very fast — you essentially just run a computer algorithm, and you can identify many new drug leads, even with new chemical structures,” Huang noted. In fact, screening the entire NCATS library of half a million compounds for anti-SARS-CoV-2 candidates took only a few minutes.
BABM also is a transferable tool — it’s not limited to use in the NCATS compound libraries. “Anyone can use this method by applying any biological activity profile data, including publicly available NCATS data,” Huang emphasized.
The NCATS researchers predict their activity-based model’s impact could extend far beyond the search for COVID-19 treatments and small-molecule drug discovery. Given any substance with an available activity profile, scientists can predict its activity against a new target, for a new indication, or against a new disease.
“In addition to small molecules, this approach can be applied to biologics, antibodies, and other therapies,” Huang said. “BABM is for all drug discovery projects.”

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Diagnosing Autism in the Pandemic

#masthead-section-label, #masthead-bar-one { display: none }At HomeWatch: ‘WandaVision’Travel: More SustainablyFreeze: Homemade TreatsCheck Out: Podcasters’ Favorite PodcastsAdvertisementContinue reading the main storySupported byContinue reading the main storyThe CheckupDiagnosing Autism in the PandemicAutism spectrum disorder is often suspected when young children stand out as being different from their peers. That can be much harder in this isolated time.Credit…Yifan WuMarch 1, 2021We talk often in pediatrics about the importance of early identification and early treatment of autism spectrum disorder, with its hallmark issues of social communication problems and restricted repetitive behavior patterns. “Early” means paying particularly close attention to the behavior and development of children between ages 1 and 3, and checking in with their parents about any concerns.But what does that mean for young children who have now spent half their lives — or more — in the special circumstances of the pandemic?Dr. Heidi Feldman, a professor of developmental and behavioral pediatrics at Stanford University School of Medicine, said, “We don’t know what the impact of one year of very restricted social interaction is going to be on children.” Some of the behavior patterns that children are showing now may be the result of these strange living conditions, or they may reflect stress, trauma and the social isolation that many families have experienced, she said.Dr. Feldman said that first-time parents who have been operating in the increased isolation of the pandemic may have very limited context for appreciating where their child’s behavior falls. They’re missing the input they might usually get from teachers and child care providers.Dr. Eileen Costello, a clinical professor of pediatrics at Boston University School of Medicine and chief of ambulatory pediatrics at Boston Medical Center, said, “Especially for the really little ones, the only eyes that are on them are their parents’. They’re not seeing uncles and aunts and cousins, not in preschool.”Dr. Costello and I are co-authors of the book “Quirky Kids: Understanding and Supporting Your Child With Developmental Differences.” We use the word “quirky” to encompass children whose development does not follow standard patterns, whether or not they fit the criteria for a specific diagnosis. Some of these children will accumulate several different diagnoses as they grow and change — and as different demands are made on them in terms of academic performance and social life — and others will never fit the criteria for any specific formal diagnosis.Dr. Adiaha Spinks-Franklin, a developmental behavioral pediatrician at Texas Children’s Hospital and an associate professor at Baylor College of Medicine, said that because parents right now are at home more, sometimes they are more likely to notice unusual or concerning patterns — repetitive behaviors, or communications problems like echolalia, in which a child repeats words. This can be completely normal, and is in fact part of how children learn to talk, but it can be concerning if it’s the major part of a child’s language as the child grows. By the age of 2, children should be saying lots of their own words.When parents — or teachers or doctors — do have concerns, getting a developmental assessment done has its own complexity in the pandemic.Catherine Lord, a professor of psychiatry and education at the University of California, Los Angeles, said, “I’m doing diagnoses right now in my back yard, which is insane.” But with the protective gear that would have to be worn at the hospital, she said, “we look like we’re from outer space,” and could be too intimidating to small children.Dr. Lord said. “We do remote interviews with parents, we try to see videos of the kid, then have them come — we have a big back yard.” And they continue to use the Zoom technology, even across the yard.The standardized assessment for autism spectrum disorder can’t be done masked, because it depends on interpreting the child’s expressions and observing reactions to the examiner’s facial expressions. Dr. Lord said there is a shorter version that children can do with their parents — everyone unmasked — while the clinicians watch without being in the room. This may not be as accurate — researchers are still analyzing the data — but they are hopeful that it will be helpful in many cases.“When we see kids in clinic, we have to be masked, and if they’re over 2, they have to be masked,” Dr. Feldman said. Earlier in the pandemic, a family that was convinced that their child had autism came to the clinic. “This kid had not seen anybody other than his parents and had not been anyplace other than his home — he was so terrified — the in-person visit was very, very hard.” They used a room with a one-way mirror, so the parents could be alone with the child, and could take their masks off, but “even with that, he had such a hard time settling down.”Dr. Lord was the lead author on a review paper on autism spectrum disorder published in Nature Reviews in 2020. She emphasized the importance of early diagnosis so that children can get early help with communication: “Kids who are going to become fluent speakers, their language starts to change between 2 and 3, and 3 and 4, and 4 and 5,” Dr. Lord said. “We want to be sure we optimize what happens in those years and that’s very hard to do if people are stuck at home.”She recommended that parents request the free assessments that can be done through early intervention, in many cases now being done remotely.Developmental assessments can include remote visits. “We have gotten quite good at doing telehealth evaluations,” Dr. Feldman said. “We get the kids in their own environments and their own toys, we get to see what they do at home.”“Sometimes making the diagnosis of autism over telehealth in a very young child is incredibly challenging,” Dr. Spinks-Franklin said. “Families that don’t have access to consistent reliable high-speed internet are also impacted — a video visit may not be possible or may be interrupted.”Even before the pandemic, many families faced long waits to get those developmental assessments. “Those who are vulnerable already are always going to be more severely affected — families who already had more limited access to primary care providers or are underinsured or uninsured already had a harder time,” Dr. Spinks-Franklin said.Now, she said, the pandemic is placing those families even more at risk, because of the likelihood of economic hardship from jobs loss, underemployment or lost health care benefits. The disparities are exacerbated, and the chance of getting to the right clinic and the right health care professional go down.Right now, because families are isolated or may not have good access to medical care, neurodevelopmental problems may be being missed in these critical early years, when getting diagnosed would help children get therapy. On the other hand, some children who don’t have these underlying problems and are just reacting to the strange and often anxiety-provoking circumstances of pandemic life may mistakenly be thought to be showing signs of autism.Parents and even doctors may worry about autism spectrum disorder in children who have attention deficit hyperactivity disorder or anxiety, and who are being seen in unusual situations — in a parking lot, for example. “I’ve been undoing diagnoses,” Dr. Lord said. “It’s not surprising that a kid is looking a bit less relaxed.”Dr. Spinks-Franklin said that the pressures of the pandemic may act on children as other stresses do, and show up as more extreme behavior, such as more frequent tantrums or increased irritability.“All that bounces is not A.D.H.D.; all that flaps is not autism,” Dr. Spinks-Franklin said.What Parents Can DoTo understand whether a child’s extreme behavior represents chronic stress and increased frustration related to the hardships that families are living through, or is a sign of a neurodevelopmental disorder, it’s important to figure out whether these behaviors were present before the pandemic, Dr. Spinks-Franklin said.If parents have concerns about a child’s development or behavior, a good place to start is to talk the question through with the child’s primary care provider, who can also review the record with the parents and talk about the child’s early developmental course.If parents still have concerns, it’s reasonable to request a referral for a full developmental assessment. Early intervention, a federally mandated program, offers help and therapy if a child seems to be significantly delayed in any developmental domain, but does not make diagnoses.Some developmental markers reflect a child’s early progress with speech and language, and with social interactions. The following are adapted from “Quirky Kids.”A baby babbles by 6 months, and the babble increases in complexityBy 9 months, a baby responds to his or her nameBy 15 to 18 months, a child can say some words and follow simple directionsBy 18 months, a child can put two words togetherBy 2 ½ to 3, a child can speak in simple sentences with some fluency and inflection — a question sounds like a questionBy 4 months, babies make eye contact and respond with social smilesBy 1 year, they can point to show interest, and wave goodbyeFrom about 2, they respond to other children and can interact in games with some back-and-forthAdvertisementContinue reading the main story

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Plastic Surgeon Attends Video Traffic Court From Operating Room

AdvertisementContinue reading the main storySupported byContinue reading the main storyPlastic Surgeon Attends Video Traffic Court From Operating RoomCalifornia’s Medical Board started an investigation after Dr. Scott Green reported for the hearing on Zoom while in scrubs and with a patient on the operating table.“Yes, I’m in an operating room right now,” Dr. Scott Green, a Sacramento plastic surgeon, acknowledged during a virtual traffic court hearing last week. “I’m available for trial. Go right ahead.”Feb. 28, 2021The Medical Board of California said it was investigating a plastic surgeon who attended a video traffic court hearing from an operating room while dressed in scrubs and with a patient on the surgical table.The surgeon, Dr. Scott Green, reported by videoconference for a trial in Sacramento Superior Court on Thursday.“Hello, Mr. Green? Hi, are you available for trial?” a courtroom clerk said as Dr. Green, wearing a surgical mask and cap, appeared in a virtual square with operating room lighting fixtures visible behind him. “It kind of looks like you’re in an operating room right now.”“I am, sir,” Dr. Green replied as machines beeped in the background. “Yes, I’m in an operating room right now. I’m available for trial. Go right ahead.”The clerk advised Dr. Green that the hearing, which was reported by The Sacramento Bee, would be live-streamed on YouTube.After Dr. Green was sworn in, his camera briefly swiveled and revealed a person on an operating table.Gary Link, a Sacramento Superior Court commissioner, appeared on camera.“Unless I’m mistaken, I’m seeing a defendant that’s in the middle of an operating room appearing to be actively engaged in providing services to a patient,” Mr. Link said. “Is that correct, Mr. Green? Or should I say Dr. Green?”Dr. Green confirmed that it was.Mr. Link continued, “I do not feel comfortable for the welfare of a patient if you’re in the process of operating that I would put on a trial notwithstanding the fact the officer is here today.”Dr. Green explained that there was another surgeon in the room who could perform the surgery.But Mr. Link disagreed.“I don’t think so. I don’t think that’s appropriate,” he said, adding that he would reschedule the trial for a time when Dr. Green was not operating on a patient.“We want to keep people healthy, we want to keep them alive. That’s important,” Mr. Link said. He set March 4 as a new trial date.The reason for Dr. Green’s court appearance was unclear.Dr. Green, who has offices in Sacramento and Granite Bay, Calif., did not respond to a request for comment on Sunday. Mr. Link also could not be reached.Carlos Villatoro, a spokesman for the Medical Board of California, said the board was aware of the hearing and “will be looking into it, as it does with all complaints it receives.”The board, he said, “expects physicians to follow the standard of care when treating their patients.”Mr. Villatoro declined to offer further details, citing the legal confidentiality of complaints and investigations.As court proceedings have moved online during the coronavirus pandemic, missteps have abounded.Judges have complained about lawyers attending proceedings shirtless and defendants logging on for hearings in bikinis and even naked.In February, a lawyer who could not figure out how to turn off a filter that made him look like a kitten found himself insisting to a judge that he was not, in fact, a cat.AdvertisementContinue reading the main story

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Is One Vaccine Dose Enough After COVID-19 Infection?

Credit: iStock/Bill Oxford

For the millions of Americans now eligible to receive the Pfizer or Moderna COVID-19 vaccines, it’s recommended that everyone get two shots. The first dose of these mRNA vaccines trains the immune system to recognize and attack the spike protein on the surface of SARS-CoV-2, the virus that causes COVID-19. The second dose, administered a few weeks later, boosts antibody levels to afford even better protection. People who’ve recovered from COVID-19 also should definitely get vaccinated to maximize protection against possible re-infection. But, because they already have some natural immunity, would just one shot do the trick? Or do they still need two?

A small, NIH-supported study, published as a pre-print on medRxiv, offers some early data on this important question [1]. The findings show that immune response to the first vaccine dose in a person who’s already had COVID-19 is equal to, or in some cases better, than the response to the second dose in a person who hasn’t had COVID-19. While much more research is needed—and I am definitely not suggesting a change in the current recommendations right now—the results raise the possibility that one dose might be enough for someone who’s been infected with SARS-CoV-2 and already generated antibodies against the virus.

These findings come from a research team led by Florian Krammer and Viviana Simon, Icahn School of Medicine at Mount Sinai, New York. The researchers reasoned that for folks whose bodies have already produced antibodies following a COVID-19 infection, the first shot might act similarly to the second one in someone who hadn’t had the virus before. In fact, there was some anecdotal evidence suggesting that previously infected people were experiencing stronger evidence of an active immune response (sore arm, fever, chills, fatigue) than never-infected individuals after getting their first shots.

What did the antibodies show? To find out, the researchers enlisted the help of 109 people who’d received their first dose of mRNA vaccines made by either Pfizer or Moderna. They found that those who’d never been infected by SARS-CoV-2 developed antibodies at low levels within 9 to 12 days of receiving their first dose of vaccine.

But in 41 people who tested positive for SARS-CoV-2 antibodies prior to getting the first shot, the immune response looked strikingly different. They generated high levels of antibodies within just a few days of getting the vaccine. Compared across different time intervals, previously infected people had immune responses 10 to 20 times that observed in uninfected people. Following their second vaccine dose, it was roughly the same story. Antibody levels in those with a prior infection were about 10 times greater than the others.

Both vaccines were generally well tolerated. But, because their immune systems were already in high gear, people who were previously infected tended to have more symptoms following their first shot, such as pain and swelling at the injection site. They also were more likely to report other less common symptoms, including fatigue, fever, chills, headache, muscle aches, and joint pain.

Though sometimes it may not seem like it, COVID-19 and the mRNA vaccines are still relatively new. Researchers haven’t yet been able to study how long these vaccines confer immunity to the disease, which has now claimed the lives of more than 500,000 Americans. But these findings do suggest that a single dose of the Pfizer or Moderna vaccines can produce a rapid and strong immune response in people who’ve already recovered from COVID-19.

If other studies support these results, the U.S. Food and Drug Administration (FDA) might decide to consider whether one dose is enough for people who’ve had a prior COVID-19 infection. Such a policy is already under consideration in France and, if implemented, would help to extend vaccine supply and get more people vaccinated sooner. But any serious consideration of this option will require more data. It will also be up to the expert advisors at FDA and Centers for Disease Control and Prevention (CDC) to decide.

For now, the most important thing all of us can all do to get this terrible pandemic under control is to follow the 3 W’s—wear our masks, wash our hands, watch our distance from others—and roll up our sleeves for the vaccine as soon as it’s available to us.

Reference:

[1] Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine. Krammer F et al. medRxiv. 2021 Feb 1.

Links:

COVID-19 Research (NIH)

Krammer Lab (Icahn School of Medicine at Mount Sinai, New York, NY)

Simon Lab (Icahn School of Medicine at Mount Sinai)

NIH Support: National Institute of Allergy and Infectious Diseases

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South Africa Study Shows Power of Genomic Surveillance Amid COVID-19 Pandemic

Credit: iStock/Thomas Faull

Considerable research is underway around the world to monitor the spread of new variants of SARS-CoV-2, the coronavirus that causes COVID-19. That includes the variant B.1.351 (also known as 501Y.V2), which emerged in South Africa towards the end of 2020 [1, 2]. Public health officials in South Africa have been busy tracing the spread of this genomic variant and others across their country. And a new analysis of such data reveals that dozens of distinct coronavirus variants were already circulating in South Africa well before the appearance of B.1.351.

A study of more than 1,300 near-whole genome sequences of SARS-CoV-2, published recently in the journal Nature Medicine, shows there were in fact at least 42 SARS-CoV-2 variants spreading in South Africa within the pandemic’s first six months in that country [3]. Among them were 16 variants that had never before been described. Most of the single-letter changes carried by these variants didn’t change the virus in important ways and didn’t rise to significant frequency. But the findings come as another critical reminder of the value of genomic surveillance to track the spread of SARS-CoV-2 to identify any potentially worrisome new variants and to inform measures to get this devastating pandemic under control.

SARS-CoV-2 was first detected in South Africa on March 5, 2020, in a traveler returning from Italy. By November 2020, despite considerable efforts to slow the spread, more than 785,000 people in South Africa were infected, accounting for about half of all reported COVID-19 cases on the African continent.

Recognizing the importance of genomic surveillance, researchers led by Houriiyah Tegally and Tulio de Oliveira, University of KwaZulu-Natal, Durban, South Africa, wasted no time in producing 1,365 near-complete SARS-CoV-2 genomes by mid-September, near the end of the coronavirus’s first peak in the country. Those samples had been collected in hundreds of clinics over the course of the pandemic in eight of South Africa’s nine provinces, offering a broad picture of the spread and emergence of new variants across the country.

The data revealed three main variants, dubbed B.1.1.54, B.1.1.56, and C.1, that were responsible for 42 percent of all the infections in South Africa’s first wave. Of the 16 newly described variants, most carried single-letter changes that haven’t been identified in other countries.

The majority of changes were what scientists refer to as “synonymous,” meaning that they don’t change the structure or function of any of the virus’s essential proteins. The exception is the newly identified C.1, which includes 16 single-letter changes compared to the original sequence from Wuhan, China. One of those 16 changes swaps a single amino acid for another on SARS-CoV-2’s spike protein. That’s notable because the spike protein is a key target of antibodies and also is essential to the virus’s ability to infect human cells.

In fact, four of the most prevalent variants in South Africa all carry this same mutation. The researchers also saw three other changes that would alter the spike protein in different ways, although the significance of these for viral spread and our efforts to stop it isn’t yet clear.

Importantly, the data show that the bulk of introductions to South Africa happened early on, before lockdown and travel restrictions were implemented in late March. Subsequently, much of the spread within South Africa stemmed from hospital outbreaks. For example, an outbreak of the C.1 variant in the North West Province in April ultimately led this variant to become the most geographically widespread in South Africa by the end of August. Meanwhile, an earlier identified South African-specific variant, B.1.106, first identified in April, vanished altogether after outbreaks were controlled in KwaZulu-Natal Province, where the researchers reside.

Genomic surveillance has remarkable power for understanding the evolution of SARS-CoV-2 and tracking the dynamics of its transmission. Tegally and de Oliveira’s team notes that this type of intensive genomic surveillance now can be used on a large scale across Africa and around the world to identify new variants of SARS-CoV-2 and to develop timely measures to control the spread of the virus. They’re now working with the African CDC to expand genomic surveillance across Africa [4].

Such genomic surveillance was crucial in the subsequent identification of the B.1.351 variant in South Africa that we’ve been hearing so much about, with its potential to evade our current treatments and vaccines. By picking up on such concerning mutations early through genomic surveillance and understanding how the virus is spreading over time and space, the hope is we’ll be better informed and more adept in our efforts to get this pandemic under control.

References:

[1] Emerging SARS-CoV-2 variants. Centers for Disease Control and Prevention.

[2] Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Bhiman J, Williamson C, de Oliveira T, et al. medRxiv 2020 Dec 22.

[3] Sixteen novel lineages of SARS-CoV-2 in South Africa. Tegally H, Wilkinson E, Lessells RJ, Giandhari J, Pillay S, Msomi N, Mlisana K, Bhiman JN, von Gottberg A, Walaza S, Fonseca V, Allam M, Ismail A, Glass AJ, Engelbrecht S, Van Zyl G, Preiser W, Williamson C, Petruccione F, Sigal A, Gazy I, Hardie D, Hsiao NY, Martin D, York D, Goedhals D, San EJ, Giovanetti M, Lourenço J, Alcantara LCJ, de Oliveira T. Nat Med. 2021 Feb 2.

[4] Accelerating genomics-based surveillance for COVID-19 response in Africa. Tessema SK, Inzaule SC, Christoffels A, Kebede Y, de Oliveira T, Ouma AEO, Happi CT, Nkengasong JN.Lancet Microbe. 2020 Aug 18.

Links:

COVID-19 Research (NIH)

Houriiyah Tegally (University of KwaZulu-Natal, Durban, South Africa)

Tulio de Oliveira (University of KwaZulu-Natal)

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