Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
This is a pre-edited, preliminary and full length version of the article. Given the gravity of the circumstances it is posted as a public service by the co-authors who are Board Members of the LSINJ as well as by the Editor of Squash Mad magazine.
(How and when should we begin playing Squash? As with everything in the post COVID-19 world – considering the stakes – very slowly and carefully!)
Kholis Abdurachim Audah Ph.D. $ , Dickson Achimugu Musa Ph.D. # , David Adebayo, Marine Engineer Diplomate, Syed Mahmood Ahmed Ph.D., Alex Diaz Ph.D., Abhishek Gupta Ph.D., Percy Ichchaporia M.S., Anthony Lai M.B.B.S., M.D., F.A.C.O.G., Lori McGrew Ph.D. ++ , Moyosola Otusanya M.S., Elizabeth Parrish, Jean Plante, Bioethicist, Consultant @ , Asmaa Rabit D.G.M.; D., Ralph Sherman B.S., Sina Varmaghani M.S., Collin C. White B.S., Nirmali Wijegoonawardana Ph.D., Rebecca Xu, Hafiz Yahya Ph.D., Poorna C.R. Yalagala Ph.D., Osama Youssef Ph.D., Alan Thatcher +1,% , George Perry Ph.D. +2,% , Ferez Soli Nallaseth, MS., Ph.D. ;,+3,%
Abstract
There are many and continuously emerging dimensions to the SARS-CoV-2 virus and the COVID – 19 Pandemic that it has caused. They go far beyond the boundaries of Health, Medical and Economic causes and consequences. No human activity, which includes Squash, is carried out in isolation and so remains unaffected by these dimensions driving the Pandemic. Breaking minimal constraints and crossing basic boundaries has societal consequences, but particularly so for personnel in the Essential and Health Services who risk their lives to ensure the safety and well-being of their fellow humans – every hour and every day! We review a small and representative segment of all these dimensions included as links from a diversity of sources that document the progression as well as the consequences of the COVID – 19 Pandemic for Humankind.
Co- author contributions and affiliations:
With the exception of the first two and the last five co-authors all non – annotated co-authors are Board Members of the LSINJ in alphabetical order, $ President Swiss German University, Indonesia, VP – Science (Asia) & Director of LSINJ Field Operations in Indonesia; # Deputy Dean, Ibrahim Badamasi Babangida (IBB) University, Lapai, Nigeria,VP – Science (Africa) & Director of Sub Saharan Institute for Diseases & LSINJ Field Operations in Africa; @ Expert: Literature Survey; Professor of Pharmacology and Director of Biochemistry and Molecular Biology, Lincoln Memorial University’s DeBusk College of Osteopathic Medicine, Executive VP LSINJ; +1,% Editor Squash Mad and Corresponding Co-Author, +2,% Dean Emeritus &; Professor of Neurosciences, UT San Antonio, TX, USA, Former Vice President for Executive Decisions in the LSINJ, corresponding co-author and Scientific Editor; &,+3,%, * Founding President, CEO, CSO & CFO for the LSINJ, principal and corresponding co-author and Scientific Editor.
Posted with permission from Co-author, Publisher, Editor and Owner Alan Thatcher to be extracted as serialized versions of the article published in Squash Mad magazine (https://squashmad.com/ ).
Caring for the sickest COVID-19 patients: An ICU story
Reporter: Gail S. Thornton, M.A.
Author Tracie White Published on November 10, 2020
When the coronavirus pandemic first took hold in the United States in early spring, there were so many unknowns.
“It was nerve-wracking,” said Dwayne Free, one of the front-line respiratory therapists who treated the first patients to arrive in the Stanford Hospital intensive care unit. “There were so many questions around how the virus was spread. People were scared. Were there going to be enough ventilators? Enough personal protection equipment? Are we doing everything right?”
In an article for the latest issue of Stanford Medicine magazine, I provide a glimpse into the journey Free and his front-line Stanford Health Care colleagues took — from Day 1 through the following weeks and months — to provide the best care for patients who were severely ill with the mysterious new disease.
Starting from scratch
As the story describes: “No one on the ICU had cared for patients with this illness before. There were no standardized treatment guidelines, and very little reliable research existed. Mostly, there were just rampant rumors of high mortality rates and even higher levels of contagion. The ICU team had to start from scratch.”
Respiratory therapist Dwayne Free and Chiara Stetson, RN, in Stanford Hospital’s ICU.
The obstacles were many and the quest for answers kept them up at night.
The extremely contagious nature of the disease meant family members had to stay away from their loved ones, further complicating care and recovery.
The personal protective equipment — more than most health care workers had ever worn — slowed them down, kept them overheated and separated them from the human-to-human contact that is so helpful in patient care.
Many of the health workers feared bringing the disease home to their families. And they faced a constant barrage of new, and untested research about treatment.
But these obstacles also brought the health professionals closer as a team, to debate best practices and share firsthand experience learning as they went. Caregivers all brought their own levels of expertise, and they needed to listen to each other if they hoped to succeed.
Sharing expertise to find solutions
A team of 50 health care workers, including physicians from a variety of specialties, nurses and respiratory therapists, began to meet via video conference in the early mornings to share new information and research. Those meetings continue today.
Along the way, the team has found reasons to celebrate and mark successes big and small — moments of joy that have kept them going.
In the article, Maureen Fay, a registered nurse and director of clinical services for Stanford Health Care, talks about the deep sense of camaraderie among the ICU staff that grew out of a shared mission to save lives during the pandemic.
“For those first couple of patients who made it out of the ICU after 30 or 40 days, everyone — nurses, respiratory therapists and doctors — lined the hallway,” she said. “They were cheering. They were so proud.”
Images by Steve Fisch. In top photo, anesthesiologist Javier Lorenzo, MD, checks on a COVID-19 ICU patient.
A study has found that front-line health care personnel (HCP) who had a positive antibody test for SARS-CoV-2 infection had asymptomatic or minimally symptomatic illness, and often didn’t believe they had COVID-19.
The results show the importance of reducing clinical thresholds for testing, and ensuring HCP have adequate personal protective equipment (PPE), the report said (MMWR Morb Mortal Wkly Rep 2020;69[35]:1221-1226).
“This suggests that performing screening tests for SARS-CoV-2 only on symptomatic health care personnel may leave a lot of cases undetected and that screening approaches that do not rely on the disclosure of symptoms may be useful in some situations,” Wesley H. Self, MD, an associate professor of emergency medicine at Vanderbilt University School of Medicine, in Nashville, Tenn., said.
The study was carried out by the Influenza Vaccine Effectiveness in the Critically Ill (IVY) Network, which includes academic medical centers in the United States conducting epidemiological studies on influenza and COVID-19. Serum specimens were collected from 3,248 front-line HCP working at 13 medical centers in 12 states in the IVY Network.
Although 6% of the participants had positive test results for SARS-CoV-2 antibodies, 29% reported no symptoms of illness since Feb. 1, 2020; 44% did not believe that they previously had COVID-19; and 69% did not report a previous COVID-19 diagnosis.
“These results show that a large proportion of health care personnel who were infected with SARS-CoV-2 in the first several months of the pandemic in the U.S. did not know they had been infected,” Self added.
In addition, seroprevalence was found to be lower among HCP who reported always wearing face coverings while interacting with patients, compared with those who did not. And those HCP who reported a shortage of PPE at their medical centers were more likely to have detectable SARS-CoV-2 antibodies than those who did not (9% vs. 6%).
The epidemiologists stressed that future spread of COVID-19 within hospitals may be mitigated by the universal use of face coverings, the development of dedicated cohorts of HCP caring for patients with COVID-19, maintaining robust supplies of PPE, and frequently testing front-line HCP.
Personalized medicine is the future of health care. Two Trump administration proposals could stymie it
Reporter: Gail S. Thornton, M.A.
By EDWARD ABRAHAMS
SEPTEMBER 25, 2020
“It is more important to know what kind of patient the disease has than to know what kind of disease the patient has.”
Although Hippocrates made this keen observation more than 2,400 years ago, physicians did not have the tools to decipher the biological and environmental factors influencing an individual’s health and well-being until recently.
Since the human genome was finally mapped in 2003, scientists have made tremendous progress in advancing personalized medicine. By tailoring health care to an individual’s biological characteristics, circumstances, and values, personalized medicine can bring unprecedented benefits to patients with rare genetic disorders, cancer, and other diseases.
But two recent moves by the Trump administration threaten to turn back the clock on biomedical progress in personalized medicine, which most Americans want, by locking us into a one-size-fits-all world.
In an executive order issued in mid-September, President Trump proclaimed his intention to cut drug prices by promising to tie what Medicare pays for prescription medications to their generally lower costs in other countries. These costs are most often based on crude one-size-fits-all health technology assessments.
The order would have a devastating effect on the future of personalized medicine and on patients’ access to lifesaving new drugs. By limiting the return on high-risk investment, it will make it more difficult for biopharmaceutical companies to bet on developing paradigm-changing products, including promising gene and cell-based therapies that may one day be able to cure, not just treat, sickle cell anemia, rare genetic disorders, some cancers, and other diseases.
The executive order was issued less than a month after the Department of Health and Human Services proposed eliminating the Food and Drug Administration’s authority to regulate laboratory-developed tests. That move may unfortunately decrease public confidence in groundbreaking diagnostic tests that have not undergone governmental review just when they are on the precipice of being able to predict cancer and Alzheimer’s disease in advance of the appearance of symptoms, when prevention and treatment plans may be more effective.
Drug pricing could and should encourage drug developers to focus on developing products that will deliver the most benefits to patients and society. Instead, in an effort to end what the president calls “global freeloading,” his executive order on pharmaceutical pricing would link the rates the Centers for Medicare and Medicaid Services pays for drugs covered under Medicare Parts B and D to the lower rates established by other developed countries. These rates are set using health technology assessments that typically do not acknowledge the heterogeneity of treatment effects, despite a rapidly expanding body of scientific evidence demonstrating that the effects of a drug often vary considerably among different subpopulations of patients.
Thus, at a moment when advanced data analytics, artificial intelligence, and real-world evidence are yielding unprecedented insights about which patients should receive which therapies, international reference pricing will rob the United States of an opportunity to stay ahead of its peers by establishing value-based payment rates for therapies that move us away from one-size-fits-all, trial-and-error medicine and toward personalized medicine.
The HHS announcement states that the FDA cannot require regulatory review of diagnostic tests developed by laboratories unless the agency allows for a rigorous regulatory process known as notice-and-comment rulemaking. Although the policy was designed to ensure that tests for Covid-19 come to market as quickly as possible, it appears to apply to the regulation of all laboratory-developed tests, including those that report genetic variants that may affect the risk of developing a disease or guide the selection of a treatment.
The 252-word statement — which comes during an as-yet unresolved bipartisan debate in Congress regarding the regulation of laboratory-developed tests — has heightened the concerns of some who contend that the success of high-risk genetic- and genomic-based tests depends on FDA review.
The potential unintended consequences of the president’s executive order and HHS’s announcement underline the importance of making careful decisions even during times of crisis. To avoid locking the United States into a one-size-fits-all world, officials at HHS would do well to support ongoing efforts by Congress to develop a clearly defined and adequately vetted regulatory framework for laboratory-developed tests. And any change in pharmaceutical pricing policies should be implemented through a transparent process that engages leaders from every sector of the health care system to ensure that, in addition to addressing cost considerations, it actually meets the needs of patients, particularly in addressing unmet medical needs.
Taking these prudent steps will help ensure that we do not foreclose a brighter future for patients and health systems in which treatments are matched to the patients who will benefit from them.
Edward Abrahams is the president of the Personalized Medicine Coalition, an education and advocacy organization in Washington, D.C.
This story is part of “Six Months In,” a special weeklong Elemental series reflecting on where we’ve been, what we’ve learned, and what the future holds for the Covid-19 pandemic.
One of the most challenging aspects of the ongoing coronavirus pandemic is that even six months in so much is still unknown and uncertain. While it can feel like the leaders tasked with navigating the pandemic are ill-equipped and unprepared (specifically in the United States), the fact remains that there are many scientists, doctors, and health leaders who are well-trained in pandemic response and have been working on the front lines of the Covid-19 pandemic since the beginning.
As government leaders and agencies have become increasingly politicized, untrustworthy, and silenced, people are turning to other sources online for up-to-date and science-backed information and guidance. In some cases, these sources have been sharing pandemic insights for years. In others, experts have realized the need for more evidence-based information on Covid-19 and have started sharing that with followers more regularly.
“Given the challenge with communications during this pandemic, and given that certain institutions have significant political limitations that impact the scope of their communications, such as CDC, the role of scientists and doctors to help fill that gap is immense,” Abraar Karan, MD, an internal medicine doctor at the Brigham and Women’s Hospital said earlier this year. “In that way, I feel like my relationship with social media has changed because there is a lot more weight and consequence to everything I write or tweet, and I take that very seriously.”
Elemental created this list of 50 health and science experts to help you separate truth from misinformation and stay up to date. These experts regularly share science-backed information and insights on the Covid-19 pandemic and/or highlight the forces and structures that influence the virus’s impact. These are also people who are very active on Twitter, and you will gain Covid-19 insights from following them online. They are ranked in alphabetical order.
Please click on the link below to view the health and science experts.
What if the First Coronavirus Vaccines Aren’t the Best?
Dozens of research groups around the world are playing the long game, convinced that their experimental vaccines will be cheaper and more powerful than the ones leading the race today.
Seven months into the coronavirus crisis, with more than 30 vaccines rapidly advancing through the rigorous stages of clinical trials, a surprising number of research groups are placing bets on some that have not yet been given to a single person.
The New York Times has confirmed that at least 88 candidates are under active preclinical investigation in laboratories across the world, with 67 of them slated to begin clinical trials before the end of 2021.
Those trials may begin after millions of people have already received the first wave of vaccines. It will take months to see if any of them are safe and effective. Nevertheless, the scientists developing them say their designs may be able to prompt more powerful immune responses, or be much cheaper to produce, or both — making them the slow and steady winners of the race against the coronavirus.
“The first vaccines may not be the most effective,” said Ted Ross, the director of the Center for Vaccines and Immunology at the University of Georgia, who is working on an experimental vaccine he hopes to put into clinical trials in 2021.
Many of the vaccines at the front of the pack today try to teach the body the same basic lesson. They deliver a protein that covers the surface of the coronavirus, called spike, which appears to prompt the immune system to make antibodies to fight it off.
In March, Dr. Veesler and his colleagues designed a vaccine that consists of millions of nanoparticles, each one studded with 60 copies of the tip of the spike protein, rather than the entire thing. The researchers thought these bundles of tips might pack a stronger immunological punch.
When the researchers injected these nanoparticles into mice, the animals responded with a flood of antibodies to the coronavirus — much more than produced by a vaccine containing the entire spike. When the scientists exposed vaccinated mice to the coronavirus, they found that it completely protected them from infection.
The researchers shared their initial results this month in a paper that has yet to be published in a scientific journal. Icosavax, a start-up company co-founded by Dr. Veesler’s collaborator, Neil King, is preparing to begin clinical trials of the nanoparticle vaccine by the end of this year.
U.S. Army researchers at the Walter Reed Army Institute have created another spike-tip nanoparticle vaccine, and are recruiting volunteers for a clinical trial that they also plan to start by the end of 2020. A number of other companies and universities are creating spike-tip-based vaccines as well, using recipes of their own.
Research at a lab of the French vaccine maker Valneva, which is taking a conventional approach to developing a vaccine, using viruses that are inactivated by chemicals.Credit…Jean-Francois Monier/Agence France-Presse — Getty Images
Antibodies are only one weapon in the immune arsenal. Blood cells known as T cells can fight infections by attacking other cells that have been infiltrated by the virus.
“We still don’t know which kind of immune response will be important for protection,” said Luciana Leite, a vaccine researcher at Instituto Butantan in São Paulo, Brazil.
It’s possible that vaccines that arouse only antibody responses will fail in the long run. Dr. Leite and other researchers are testing vaccines made of several parts of the coronavirus to see if they can coax T cells to fight it off.
“It’s a second line of defense that might work better than antibodies,” said Anne De Groot, the C.E.O. of Epivax, a company based in Providence, R.I.
Epivax has created an experimental vaccine with several pieces of the spike protein, as well as other viral proteins, which it plans to test in a clinical trial in December.
The effectiveness of a vaccine can also be influenced by how it gets into our body. All of the first-wave vaccines now in clinical trials have to be injected into muscle. A nasal spray vaccine — similar to FluMist for influenza — might work better, since the coronavirus invades our bodies through the airway.
Several groups are gearing up for clinical trials of nasal spray vaccines. One of the most imaginative approaches comes from a New York company called Codagenix. They are testing a vaccine that contains a synthetic version of the coronavirus that they made from scratch.
The Codagenix vaccine is a new twist on an old formula. For decades, vaccine makers have created vaccines for diseases such as chickenpox and yellow fever from live but weakened viruses. Traditionally, scientists have weakened the viruses by growing them in cells of chickens or some other animal. The viruses adapt to their new host, and in the process they become ill-suited for growing in the human body.
The viruses still slip into cells, but they replicate at a glacial pace. As a result, they can’t make us sick. But a small dose of these weakened viruses can deliver a powerful jolt to the immune system.
Yet there are relatively few live weakened viruses, because making them is a struggle. “It’s really trial-and-error based,” said J. Robert Coleman, the chief executive of Codagenix. “You can never say exactly what the mutations are doing.”
The Codagenix scientists came up with a different approach. They sat down at a computer and edited the coronavirus’s genome, creating 283 mutations. They then created a piece of DNA containing their new genome and put it in monkey cells. The cells then made their rewritten viruses. In experiments on hamsters, the researchers found that their vaccine didn’t make the animals sick — but did protect them against the coronavirus.
Codagenix is preparing to open a Phase 1 trial of an intranasal spray with one of these synthesized coronaviruses as early as September. Two similar vaccines are in earlier stages of development.
The French vaccine maker Valneva plans to start clinical trials in November on a far less futuristic design. “We are addressing the pandemic with a rather conventional approach,” said Thomas Lingelbach, the C.E.O. of Valneva.
Valneva makes vaccines from inactivated viruses that are killed with chemicals. Jonas Salk and other early vaccine makers found this recipe to work well. Chinese vaccine makers already have three such coronavirus vaccines in Phase 3 trials, but Dr. Lingelbach still sees an opportunity for Valneva making its own. Inactivated virus vaccines have to meet very high standards for purification, to make sure all the viruses are not viable. Valneva has already met those standards, and it’s not clear if Chinese vaccines would.
The United Kingdom has arranged to purchase 60 million doses of Valneva’s vaccine, and the company is scaling up to make 200 million doses a year.
Faster and cheaper production
Work on a vaccine assembly line at the Serum Institute in Pune, India. Credit…Atul Loke for The New York Times
Even if the first wave of vaccines work, many researchers worry that it won’t be possible to make enough of them fast enough to tackle the global need.
“It’s a numbers game — we need a lot of doses,” said Florian Krammer, a virologist at Icahn School of Medicine at Mount Sinai in New York City.
Some of the most promising first-wave products, such as RNA vaccines from Moderna and Pfizer, are based on designs that have never been put into large-scale production before. “The manufacturing math just doesn’t add up,” said Steffen Mueller, the chief scientific officer of Codagenix.
Many of the second-wave vaccines wouldn’t require a large scale-up of experimental manufacturing. Instead, they could piggyback on standard methods that have been used for years to make safe and effective vaccines.
Codagenix, for example, has entered into a partnership with the Serum Institute of India to grow their recoded coronaviruses. The institute already makes billions of doses of live weakened virus vaccines for measles, rotaviruses and influenza, growing them in large tanks of cells.
Tapping into well-established methods could also cut down the cost of a coronavirus vaccine, which will make it easier to get it distributed to less wealthy countries.
Researchers at Baylor College of Medicine, for example, are doing preclinical work on a vaccine that they said might cost as little as $2 a dose. By contrast, Pfizer is charging $19 a dose in a deal with the U.S. government, and other companies have floated even higher prices.
To make the vaccine, the Baylor team engineered yeast to make coronavirus spike tips. It’s precisely the same method that has been used since the 1980s to make vaccines for hepatitis B. The Indian vaccine maker Biological E has licensed Baylor’s vaccine and is planning Phase 1 trials that will start this fall.
“They now already know they can make a billion doses a year,” said Maria Elena Bottazzi, a Baylor virologist. “It’s easy-breezy for them, because it was exactly the same bread-and-butter vaccine technology that they have been working with for years.”
Even if the world gets cheap, effective vaccines against Covid-19, that doesn’t mean all of our pandemic worries are over. With an abundance of other coronaviruses lurking in wild animals, another Covid-like pandemic may be not far off. Several companies — including Anhui Zhifei in China, Osivax in France and VBI in Massachusetts — are developing “universal” coronavirus vaccines that might protect people from an array of the viruses, even those that haven’t colonized our species yet.
Many scientists see their ongoing vaccine work as part of a long game — one that the well-being of entire nations will depend on. Thailand, for example, is preparing to purchase Covid-19 vaccines developed overseas, but scientists there are also carrying out preclinical research of their own.
At Chulalongkorn University, researchers have been investigating several potential candidates, including an RNA-based vaccine that will go into Phase 1 studies by early 2021. The vaccine is similar to one that Pfizer is now testing in late-stage clinical trials, but these scientists want the security of making their own version.
“While Thailand has to plan for buying vaccines, we should do our best to produce our own vaccine as well,” said Kiat Ruxrungtham, a professor at Chulalongkorn University. “If we are not successful this time, we will be capable to do much, much better in the next pandemic.”Correction: Aug. 27, 2020
An earlier version of this article misstated which animals had been protected by the nanoparticle vaccine in development at the University of Washington. It was vaccinated mice, not vaccinated monkeys.
Carl Zimmer writes the “Matter” column. He is the author of thirteen books, including “She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity.” @carlzimmer • Facebook
On Feb. 26, 175 executives at the biotech company Biogen gathered at a Boston hotel for the first night of a conference. At the time, the coronavirus seemed a faraway problem, limited mostly to China.
But the virus was right there at the conference, spreading from person to person. A new study suggests that the meeting turned into a superspreading event, seeding infections that would affect tens of thousands of people across the United States and in countries as far as Singapore and Australia.
The study, which the authors posted online on Tuesday and has not yet been published in a scientific journal, gives an unprecedented look at how far the coronavirus can spread given the right opportunities.
“It’s a really valuable study,” said Dr. Joshua Schiffer, a physician and mathematical modeling expert who studies infectious diseases at the Fred Hutchinson Cancer Research Center in Seattle and was not involved in the research.
Dr. Schiffer said that the new genetic evidence fit well with what epidemiologists and disease modelers have been learning about the coronavirus. The Biogen conference, he said, was just one of many similar events that amplified and spread the virus in its early months. “I don’t think it’s a fluke at all,” he said.
The results came out of a project that began in early March at the Broad Institute of Harvard and M.I.T., a research center specializing in large-scale genome sequencing. As a wave of Covid-19 patients crashed into Massachusetts General Hospital, the Broad researchers analyzed the genetic material of the viruses infecting the patients’ cells. The scientists also looked at samples from the Massachusetts Department of Public Health, which ran tests around Boston at homeless shelters and nursing homes. All told, the scientists analyzed the viral genomes of 772 people with Covid-19 between January and May.
The researchers then compared all of these genomes to trace where each virus came from. When a virus replicates, its descendants inherit its genetic material. If a random mutation pops up in one of its genes, it will also get passed down to later descendants. The vast majority of such mutations don’t change how the virus behaves. But researchers can use them to track the spread of an epidemic.
“It’s kind of like a fingerprint we can use to follow viruses around,” said Bronwyn MacInnis, a genomic epidemiologist at the Broad Institute.
The first confirmed case of the coronavirus in Boston turned up on Jan. 29. The patient had traveled from Wuhan, China, and his virus carried distinctive mutations found in Wuhan. But Dr. MacInnis and her colleagues didn’t find any other viruses in Boston from later months with the same genetic fingerprint. It’s likely that the patient’s isolation prevented the virus from spreading.
But as February rolled on, the researchers determined, at least 80 other people arrived in Boston with the virus. Undiagnosed, they spread it to others.
Most of the viral lineages in Boston have a genetic fingerprint linking them to earlier cases in Europe, the study found. Some travelers brought the virus directly from Europe in February and March, whereas others may have picked up the European lineage elsewhere in the northeastern United States.
Dr. MacInnis and her colleagues took a detailed look at a few key places to see how the virus swept through the city. At Massachusetts General Hospital, for example, they found that coronaviruses in patients did not share many of the same mutations. That was a relief, because it meant that the hospital was not a breeding ground where a single virus could spread quickly from patient to patient.
But that’s exactly what happened in a skilled nursing home where 85 percent of patients and 37 percent of the staff were infected. The researchers identified three different virus lineages in the home, but one of them accounted for 90 percent of the infections.
Such superspreading events are a hallmark of the coronavirus. When an infected person shows up in the right place — generally inside, with poor ventilation and close contact with other people — the virus can infect a lot of people in very little time. These unfortunate events don’t happen often, and so most people who get infected with the coronavirus don’t pass it on to anyone else.
The virus that raged through the nursing home didn’t spread beyond its walls, as far as Dr. MacInnis and her colleagues could tell. But when the virus showed up at the Biogen conference, the story turned out very differently.
The researchers were able to sequence 28 viral genomes from people at the meeting. All of them shared the same mutation, called C2416T. The only known samples with that mutation from before the Biogen event came from two people in France on Feb. 29.
It’s possible that a single person came to the meeting from Europe carrying the C2416T mutation. It’s also possible that the virus carrying this mutation had already been in Boston for a week or two, and someone brought it into the meeting.
As the attendees spent hours together in close quarters, in poorly ventilated rooms, without wearing masks, the virus thrived. While replicating inside the cells of one meeting attendee, the virus gained a second mutation, called G26233T. Everyone who was subsequently infected by that person carried the double-mutant virus.
From the meeting, the researchers concluded, this lineage spread into the surrounding community. In a Boston homeless shelter, for example, researchers found 51 viral samples with the C2416T mutation, and 54 with both mutations.
“We had no idea it would be associated with the conference,” Dr. MacInnis said. “It came as a complete surprise.”
The researchers estimated that roughly 20,000 people in the Boston area could have acquired the conference virus.
New York saw a similar pattern, according to Matthew Maurano, a computational biologist at N.Y.U. Langone Health. After many viral strains arrived from Europe in February, a few came to dominate the city. “A lot of lineages die off, and some spread enormously,” Dr. Maurano said.
The Boston double-mutant spread particularly far. Researchers identified this lineage in samples collected later in Virginia, North Carolina and Michigan. Overseas, it turned up in Europe, Asia and Australia.
Dr. Jacob Lemieux, a co-author of the new study and an infectious disease physician at Massachusetts General Hospital, said it was impossible at the moment to determine how many people acquired the virus in the months after the Biogen conference. But it would be in the tens of thousands.
Six months after the conference, Dr. MacInnis said that it should serve as a warning to anyone who thinks life can return to an unmasked version of normal before the virus is brought under control.
“One bad decision can affect a lot of people,” she said. “And the ones who suffer the most from that reality are the most vulnerable among us.”
Carl Zimmer writes the “Matter” column. He is the author of thirteen books, including “She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity.”
‘But I Saw It on Facebook’: Hoaxes Are Making Doctors’ Jobs Harder
Reporter: Gail S. Thornton, M.A.
Without the support of social platforms, our efforts to stamp out viral misinformation feel futile.
By Seema Yasmin and Craig Spencer
Dr. Yasmin is the author of “Viral B.S.: Medical Myths and Why We Fall for Them.” Dr. Spencer is an emergency medicine physician.Aug. 28, 2020
August 28, 2020
Credit…Kiersten Essenpreis
The news came from a colleague — not a doctor but someone who works in the emergency room and has seen firsthand the devastation caused by the pandemic. “There is a cure for Covid-19,” he said. “It must be true because a doctor friend shared a Facebook post about this cure.”
When confronted with the latest, credible scientific evidence — that there is no cure for Covid-19, that the disease has killed more than 180,000 Americans precisely because we have no effective way of averting death for the millions who are infected — he doubled down. “But I saw it on Facebook,” he said.
In the emergency room and in conversations with the American public through cable news interviews and Op-Eds like this one, we’ve both been working to dissect and debunk the many myths about this new virus, its potential treatments and the possibility of a vaccine. We read the mistruths on our patient’s phones, listen to theories borrowed from internet chat rooms and watch as friends and family scroll through Facebook saying, “Here — it says that this was definitely created in a Chinese laboratory.”
Seven months into the worst pandemic of our lifetime, the virus continues to spread alongside medical myths and health hoaxes. False news is not a new phenomenon, but it has been amplified by social media. A new report about Facebook from Avaaz, a nonprofit advocacy organization that tracks false information, shows how widespread and pervasive this amplification is.
Websites spreading health hoaxes on Facebook peaked at an estimated 460 million views on the platform in April 2020, according to the report, just as the virus was spreading around the world and overwhelming hospitals in New York City. Facebook claims to assess and add warning labels to factually incorrect posts; but in a subset of posts analyzed by Avaaz, only 16 percent of those containing health misinformation had a warning label.
Facebook’s algorithm rewards and encourages engagement with content that provokes strong emotions, which isexactly the kind of content we warn patients to doubt and carefully assess, since false information is often packaged as novel and sensational. The report’s title calls Facebook’s algorithm “A Major Threat to Public Health” — something our clinical and research experiences amply confirm.
Public health organizations have been unable to keep up with the deluge of sophisticated medical myths and pseudoscience shared on Facebook. Despite the efforts of the Centers for Disease Control and Prevention and the World Health Organization, content from the top 10 health misinformation sites received four times as many Facebook views as content from the C.D.C., W.H.O. and eight other leading health institutions during April 2020.
Facebook enables known misinformation spreaders to share their bunk widely. Networks spreading health conspiracy theories and pseudoscience generated an estimated 3.8 billion Facebook views between May 28, 2019 and May 27, 2020.
The report quantifies the reach of so-called superspreaders of health misinformation and disinformation on Facebook, including websites such as GreenMedInfo and RealFarmacy, which package pseudoscience as credible, believable news. These include false claims that 5G technology is harmful to human health and that certain types of vaccines have never been tested.
While GreenMedInfo has been removed from Pinterest, it thrives on Facebook: In the last year, it received more than 39 million views. And RealFarmacy, which according to Avaaz is on track to become one of the largest health misinformation networks in the world, received an astonishing 581 million views in a year. One article alone, hawking colloidal silver as a treatment for viruses, was viewed an estimated 4.5 million times. We can’t compete with a global platform whose powerful algorithm rewards sensational, false content.
We see the consequences in the clinic and the emergency room. Patients question our evidence-based medical guidance, refuse safe treatments and vaccines, and cite Facebook posts as “proof” that Covid-19 is not real.
While doctors and other health care professionals play a critical role in educating the public, we are not immune to the sophisticated techniques of false information. Colleagues have confided in us that they believe the virus is man-made and diminishing in strength; others have asked us to invest money in Covid-19 “cures.” While we try, each day, to counter these dangerous falsehoods that circulate among our patients and our peers, our ability to counsel and provide care is diminished by a social network that bolsters distrust in science and medicine. Facebook is making it harder for us to do our jobs.
Seema Yasmin (@DoctorYasmin) is director of the Stanford Health Communication Initiative and the author of the forthcoming, “Viral B.S.: Medical Myths and Why We Fall for Them.” Craig Spencer (@Craig_A_Spencer) is an emergency medicine physician and director of Global Health in Emergency Medicine at NewYork-Presbyterian/Columbia University Medical Center.
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8/11/2020
Infectious: How COVID Killed My Colleague-Patient; I Was Right; Attacked by Anti-Vaxxers
Stories from three doctors about when things get infectious
Reporter: Gail S. Thornton, M.A.
You’re joining us on Anamnesis, a podcast about medicine … but the things about medicine that aren’t drugs and protocols and studies, the things about medicine that are hard to articulate, that make us come back for more, that keep us engaged in this crazy, mixed-up world we get to participate in, called “caring.” Caring for patients, caring for the health of our nation, and caring about our fellow man/woman in healthcare. Care has been more important than ever with everything going on.
by Amy Faith Ho, MD August 7, 2020
On Anamnesis, we strive to give you relief, context, and insight into our field, which is more important now than ever. Our theme is super appropriate, as are our guests in this episode titled “Infectious.”
Underprotected Clinicians: ‘We are tired of Advocating’
Reporter: Gail S. Thornton, M.A.
John Whyte, MD, MPH; Esther Choo, MD, MPH
July 24, 2020
There is a shortage of personal protective equipment (PPE) in hard-hit states like Arizona, Florida, and Texas. It has been difficult to fulfill their PPE requests because of supply chain issues and underestimating the sustained PPE need.
As schools reopen this fall, there will be an increased need for PPE to protect teachers and staff.
Healthcare worker burnout, stress, anxiety, and PTSD have increased substantially during the pandemic.
Our society stigmatizes clinicians who admit that they have mental health issues, and they can be penalized professionally for seeking help.
Clinicians need mental health services that are widespread, easily accessible, and confidential.
This transcript has been edited for clarity.
John Whyte, MD, MPH: You’re watching Coronavirus in Context. I’m Dr John Whyte, chief medical officer at WebMD. Today I’m joined by Dr Esther Choo, professor of emergency medicine at Oregon Health and Science University Medical Center in Lake Oswego, Oregon. Dr Choo, thanks for joining us again.
Esther Choo, MD, MPH: Thanks for having me on.
Whyte: You helped shed light on what was happening on the front lines, especially in terms of shortages of PPE as well as burnout. What’s happening now on the front lines?
Choo: I have seen things that are hopeful but also very discouraging. In many ways this has been a Groundhog Day era, where I wake up and think, Are we in March? April? Because here we are in July, and many of the same issues are present.
Certainly, we’ve done a lot of work, but there are concerning shortages in the resources that we need. For example, through the organization I’m involved with, GetUsPPE.org, we’ve distributed more than 2 million units of PPE around the country. We have requests pouring in from the hardest-hit areas right now (eg, Arizona, Florida, and Texas), and we’ve only been able to meet about 10% of the need there. So that represents a lot of work and a lot of successful distribution of PPE. At the same time, we are constantly overwhelmed with a huge need that’s out there, particularly for smaller health facilities.
Whyte: Why do you think it’s the case? Is it an issue of manufacturing, that companies just can’t make PPE quick enough? Is it poor coordination at the federal and state levels in terms of getting it to people who need it? It seems like we made some progress in terms of providing PPE to frontline responders. As you point out, we’re now heading back to areas experiencing shortages. How can we fix it?
Choo: It’s everything from failing to mobilize the supply chain, from underestimating the amount of need — and the sustained need. Back in February and March, we didn’t imagine that we would still be here in mid-summer with rates going up and hospitals either in crisis now or heading into one.
As we reopened, there was a need for PPE in many locations and businesses that were not hospitals, and we failed to estimate how much PPE we need. As we go into the fall, there’s going to be a huge PPE need in schools in order to protect and keep teachers safe as we reopen the schools in many areas.
The need has marched ahead of a fairly fixed supply chain. Although, again, we’re doing as best as we can to stimulate the supply chain and to create an inflow of materials as we have them.
Whyte: What can listeners do? Could they donate? Could they help in some ways in their communities?
Choo: There are so many ways to help. Organizations like mine (GetUsPPE.org) and others are accepting donations. We put as much of that money directly in the hands of healthcare organizations, helping them boost their supplies as much as possible.
It’s important to not get “issue fatigue” here. There were so many people advocating for increased supplies ─ talking to elected officials, advocating for mobilization of federal, state, and local resources ─ so we continue to support healthcare organizations in acquiring PPE.
People got tired, which is understandable, as we are tired of advocating for it. As long as this surge continues, we need to be as energetic as the virus in advocating that resources be dedicated to this, because it’s an important part of the containment effort.
Choo: There are a lot of wonderful efforts to create online, free, accessible counseling resources for healthcare workers on the front lines and who are experiencing stress, anxiety, PTSD, and burnout.
But I want to be clear that these kinds of crisis resources are Band-Aids on top of what has been a mental health crisis in healthcare before we had a pandemic. Yes, we’re in an unprecedented time in terms of the sustained stress that this pandemic has brought, but we’re in this environment where it’s shameful to admit that you have mental health problems or that you need help from a therapist.
It is actually scary to try to seek medical care, because you can be penalized professionally. Medical boards will ask whether you’ve sought mental health care in a way that doubles down on that fear and stigma. And there can be real professional consequences. We’ve seen this.
We need to change the culture in healthcare around having mental health problems. This should be viewed as a very normal part of our very tough practices. We should try to make our healthcare environments more humane to begin with so that it’s not as harrowing to have a career in medicine. We should view seeking care as an expected and normal part of a healthcare provider’s professional life.
Whyte: What are some of the resources that people could use right now?
Choo: My own hospital does a great job of this. We have a confidential counseling service for healthcare workers; you can walk in any day of the week and receive 100% confidential and free care. I can leave a shift and walk into that office. They make themselves as accessible as possible.
Because it’s so confidential, I don’t have to be afraid to walk in there. When they see that there is a bad event in a department or something happens on social media, they do outreach and say, “Hi. It looks like you’re going through a tough time. I just want you to know that these hours are open to you.”
They’re very proactive in providing support, and that is what we need right now. We need to acknowledge a couple of things. First of all, this is a difficult time like no other. It’s layered on an already tough practice. We need to make resources so available that you cannot avoid them, which is how I honestly feel like it is at my institution.
We need to lower the bar of accessibility in every single way — in how many steps you need to go through to reach that resource. Lower the bar on cost. Lower the bar on any punitive or stigmatizing attitudes toward that care. We need that now more than ever. When the pandemic’s over, we need to completely reset how we approach these issues to begin with.
Whyte: When do you think the pandemic will be over?
Choo: I think this is going to be a long year. That’s all that I will say in terms of a school year because I have school-age kids. In my household, we are planning to not expect normality for a full calendar school year. Even if we get a vaccine in the early part of 2021, I am very concerned, based on what we’ve seen, that we can scale up our manufacturing and our distribution chains in a way that is efficient and equitable. I don’t think that we will reap the benefit of that for quite some time. I’m uncomfortably settled into a nonnormal life right now.
Whyte: You started off the interview by saying you’re hopeful. What are you hopeful about?
Choo: I’m really impressed by our community of healthcare workers and scientists. I sit here, day after day, and watch people leave their regular jobs ─ their very exhausting, taxing, and physically draining jobs. Then they sit down and they do advocacy work so that we can get the science out. I’ve never seen so many healthcare workers out there using their voices to educate the public, contributing to projects, so that we can do things like distribute PPE and educate our community.
These people are volunteering with their school systems to try to make the best and safest plan so that kids can return to school in some capacity. They’re volunteering in workplaces and trying to figure out how we can transform physical spaces so that people can be at work in some capacity. They’re joining conversations at the local, state, and national levels. Our people are showing up in droves day after day. This has become a 24/7 project, fighting the pandemic and working with people at every level in every sector to try to get through this.
I don’t know about you, but I have felt just tremendously inspired by the work that people are doing on their own time to just get our country through this. It gives me hope every single day even as so many things are devastating about this virus.
Whyte: Dr Choo, thank you for all that you are doing and for being a leader, a mentor, and an inspiration to a lot of people.
Choo: Thank you, Dr Whyte. I really appreciate it.
Whyte: And thank you for watching Coronavirus in Context.
The expert oncologist discussed the findings of the COVID-19 and Cancer Consortium and how the results of the consortium should inform conversations with patients with cancer.
In an interview with CancerNetwork®, Petros Grivas, MD, PhD, board-certified oncologist at the Seattle Cancer Care Alliance (SCCA), director of the University of Washington (UW) School of Medicine’s Genitourinary Cancers Program, and a UW professor of Oncology, spoke about advice for patients during the coronavirus disease 2019 (COVID-19) pandemic based on results from the COVID-19 and Cancer Consortium (CCC19).
Data from the consortium, presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, suggested that in patients with cancer and COVID-19, cancer that is progressing was independently associated with an increased risk of death.
Additionally, treatment with both hydroxychloroquine and azithromycin was also strongly associated with an increased risk of death.
Importantly though, longer follow-up is needed to better understand the impact of COVID-19 on outcomes in patients with cancer, including whether or not specific cancer treatments should be continued.
Transcription: I think it’s very important when we give advice to our dear patients to always put on the caution hat and make the point that this data is definitely informing, in my opinion, those discussions but are not, as I mentioned before, conclusive done deal results, because of the evolving nature of the consortium registry study. But I think the advice is, number one, have a discussion with your provider individually one by one and see how this data fit in. Specifically, in this specific patient scenario you have to think about the individual patient and the risk factors of those patients, especially in age, sex, as well as status of the cancer, type of the cancer, all of these are relevant factors to discuss with the provider.
But I think one of the take home points is that patients who need treatment for their cancer, in our experience in our cancer center and based on these data, these patients probably can go ahead and do… pursue the treatment they need in order to avoid delays in their cancer care. As the active peak, surge of the pandemic, gets more controlled, I think we’re seeing more and more patients with cancer coming in the cancer centers, which makes us a little bit worried about the volumes of patients and we always want to make sure we ensure timely and proper care. So, I think it’s important to have these discussions and institute cancer therapy early on, in a timely manner when needed.
We have underestimated and misunderstood COVID-19 since it first appeared.
And as we learn more, it’s clear that COVID-19 can be more than just a respiratory disease. It’s joined the ranks of other “great imitators” — diseases that can look like almost any condition.
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It can be a gastrointestinal disease causing only diarrhea and abdominal pain. It can cause symptoms that may be confused with a cold or the flu. It can cause pinkeye, a runny nose, loss of taste and smell, muscle aches, fatigue, diarrhea, loss of appetite, nausea and vomiting, whole-body rashes, and areas of swelling and redness in just a few spots.
In a more severe disease, doctors have also reported people having heart rhythm problems, heart failure, kidney damage, confusion, headaches, seizures, Guillain-Barre syndrome, and fainting spells, along with new sugar control problems.
It’s not just a fever and coughing, leading to shortness of breath, like everyone thought at first.
This makes it incredibly difficult to diagnose and even harder to treat.
“This is a disease progression we have never seen for any infection that I can think of, and I’ve been doing this for a couple of decades,” says Joseph Vinetz, MD, an infectious disease specialist at Yale School of Medicine.
How It Invades
When viral particles land in our eyes, nose, or mouth, “spike proteins” on the virus connect with a specific receptor, known as ACE2, on the surface of our cells, allowing entry. ACE2 receptors make a great target because they are found in organs throughout our bodies. Once the virus enters, it turns the cell into a factory, making millions and millions of copies of itself — which can then be breathed or coughed out to infect others.
In order to evade early detection, the coronavirus uses multiple tools to prevent the infected cells from calling out for help. The virus snips off distress signal proteins that cells make when they are under attack. It also destroys antiviral commands inside the infected cell. This gives the virus much more time to make copies of itself and infect surrounding areas before it is identified as an invader. This is part of the reason why the virus spreads before immune responses, like fever, begin.
Direct Attack
Many with mild or no symptoms are able to fend off the virus before it gets worse. These people may have symptoms only in the upper airway, at the site where they were first infected. But when someone’s body can’t destroy the virus at its entry point, viral particles march deeper into the body. The virus seems to take a few paths from there, either setting up camp in the lungs, fighting its way into the digestive tract, or doing some combination of both.
“There’s clearly a respiratory syndrome, and that’s why people end up in the hospital. Some people get a gastrointestinal illness with diarrhea, maybe some abdominal pain, which may or may not be associated with a respiratory illness,” says Vinetz.
COVID-19 is proving to be far more dangerous to far more parts of the body than previously believed.
Once the virus is deeply embedded in the body, it begins to cause more severe disease. This is where direct attack on other organs that have ACE2 receptors can occur, including heart muscle, kidneys, blood vessels, the liver, and potentially the central nervous system. This may be one reason for the vast array of symptoms COVID-19 can cause.
“It’s highly unlikely that any other organs can be affected through direct invasion without severe disease,” Vinetz adds.
The brain and nerves may also fall prey to direct attack. Kenneth Tyler, MD, chair of the Department of Neurology at the University of Colorado School of Medicine, cautions that direct central nervous system (CNS) attack is still being worked out at this time. There are many routes a virus could take to invade the CNS. One somewhat disputed view is that the loss of smell could indicate that the nerve responsible for smell is infected and can carry the virus into the CNS, including the brain. “This can be shown to occur in experimental models with non-human coronaviruses and is a potential route of invasion for some other viruses. However, there is no evidence to date establishing that this actually occurs with SARS-CoV-2,” the official name of the virus that causes COVID-19.
Early findings, including those from autopsy and biopsy reports, show that viral particles can be found not only in the nasal passages and throat, but also in tears, stool, the kidneys, liver, pancreas, and heart. One case report found evidence of viral particles in the fluid around the brain in a patient with meningitis.
Collateral Damage That Kills
Severe damage to the lungs may be one trigger that activates and overstimulates the immune system through a barrage of signaling chemicals, known as cytokines.
The flood of these chemicals can set off what is referred to as a “cytokine storm.” This is a complex interplay of chemicals that can cause blood pressure to drop, attract more killer immune and inflammatory cells, and lead to even more injury within the lungs, heart, kidneys, and brain. Some researchers say cytokine storms may be the cause of sudden decompensation, leading to critical illness in COVID-19 patients.
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A new finding suggests there may be another deadly culprit. Many doctors are discovering that abnormal clotting, known as thrombosis, may also play a major role in lethal COVID-19. Doctors are seeing clots everywhere: large-vessel clots, including deep vein thrombosis (DVT) in the legs and pulmonary emboli (PE) in the lungs; clots in arteries, causing strokes; and small clots in tiny blood vessels in organs throughout the body. Early autopsy results are also showing widely scattered clots in multiple organs.
Adam Cuker, MD, a hematologist at the Hospital of the University of Pennsylvania who specializes in clotting disorders, says these clots are happening at high rates even when patients are on blood thinners for clot prevention. In one study from the Netherlands, 31% of patients hospitalized with COVID-19 got clots while on blood thinners.
Cuker says that “new studies validate what we have all been seeing with our eyes, which is that ‘boy, it seems that these patients are clotting a lot.’ … And it could be that the rate of thrombotic events are even higher than we truly recognize.” Though the reason for the clotting is still not clear, it seems to be playing a much larger role in death than previously understood.
Beyond the collateral damage from cytokine storms and clotting, other things like low blood pressure that comes from a severe illness, low oxygen levels, ventilator use, and drug treatments themselves can all harm organs throughout the body, including the heart, kidneys, liver, brain, and other organs.
Double-Edged Sword
Even though researchers are learning more each day about the virus and how and where it attacks the body, treatment geared toward these targets also pose significant problems. Many drugs come with a risk of destroying the delicate balance that allows the body to help fight the disease or to manage inflammation.
The ACE2 receptor that the virus uses to enter cells is a key player in lowering inflammation and reducing blood pressure. Targeting or blocking this receptor as a treatment strategy to prevent viral entry into cells may actually worsen blood pressure, increase the risk of heart failure and kidney injury, and increase inflammation that may worsen lung injury.
Drugs that target the immune response to lower the risk of a cytokine storm may also tamp down the immune response, making it hard to kill off the virus over the long run.
Using medicines to prevent clotting may end up causing severe bleeding. Cuker points out that “we don’t have a good read on bleeding … we have limited evidence about the clotting risk … we have zero evidence on bleeding risk in these patients, and it’s a real priority to understand this risk, especially because one of our strategies to treat the clotting is stepping up intensity the of anti-coagulation.”
Timing is likely to be key in treatment strategies. For example, patients may need a drug to boost the immune system early on in the disease, and then one to tamp it down if the disease progresses and cytokine markers begin to rise.
Just the Tip of the Iceberg
Cuker says that what we know about clotting and almost everything else when it comes to COVID-19 “is just the tip of the iceberg.”
Sanober Amin, MD, PhD, a dermatologist in Texas, agrees. She’s been tracking the wide variety of skin findings that dermatologists across the world have been noting on social media.
She recently posted images on social media that show the wide variety of skin findings she has been seeing and hearing about. Her post received a massive response. Amin says that “dermatologists from around the world, from Turkey to France to Canada to the U.S., are sharing information about rashes that they’ve observed in people with COVID-19.”
Some rashes seem to be consistent with what’s called a viral exanthema, which is a term for a general rash that can happen with almost any virus. But, Amin says, “some skin findings are more consistent with superficial clotting in blood vessels close to the skin.”
This is what some have started to call “ COVID toes,” also called pernio. Dermatologists are seeing more cases of these small clots in toes and fingers, especially in children.
It’s hard to know which skin conditions are related to COVID-19 because a lot of people without “typical” symptoms are not being tested, Amin says. Researchers will still need to work out which symptoms may be caused by the virus and which may just be unrelated early findings.
Unanswered Questions
For now, much of the information we have about the symptoms of COVID-19 come from hospitalized patients who are very sick by the time they seek care and may not be able to share information about the early signs and symptoms they may have had.
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Because of the lag in testing in the U.S., we still don’t know the full extent of what mild and moderate versions of the disease look like, or what effects the disease has on people who have many symptoms but aren’t quite sick enough to be hospitalized.
One open question is what the long-term effects may be for survivors. What does life look like after being on a ventilator or suddenly needing dialysis? Will we see decreases in heart, lung, and kidney function that is long-lasting and permanent, or will patients eventually recover?
We also don’t know how people will clear infections. If the new coronavirus ends up being an acute infection, like other coronaviruses, most recovered people should develop at least a short-term immunity. It’s also possible that the virus may persist as a latent infection, like chickenpox, lying dormant in the body, only to re-emerge periodically as shingles does, or become a chronic infection, like hepatitis B, living within the body for a sustained period of time, causing long-term damage.
“It’s definitely going to be an acute infection … there’s no way it’s going to be latent or chronic, no way … I think so … we’ll see,” Vinetz says.
What Coronavirus Researchers Can Learn From Economists
Reporter: Gail S. Thornton, M.A.
Randomized controlled trials remain the gold standard, but natural experiments can help doctors who need answers now.
By Anupam B. Jena and Christopher M. Worsham
June 30, 2020
A drug that has recently been found to help some Covid-19 patients could form the basis of natural experiments.Credit…Nati Harnik/Associated Press
The recent news that a decades-old steroid drug, dexamethasone, showed a one-third reduction in mortality for patients with severe Covid-19 infections has generated immense hope in the medical community. The finding came from the Recovery trial, a large randomized controlled trial in Britain.
The reason doctors are so excited is that randomized controlled trials are the gold standard in medicine. Using randomization (by, say, flipping a coin to assign patients to a new treatment or not) is the best way to determine whether treatments work.
Unfortunately, randomized trials take time — which is a problem when doctors need answers now. So doctors and public health officials have been turning to available real-world data on patient outcomes and trying to make sense of them.
But it can be hard for doctors to find the answers they need in this observational data because without randomization, hidden biases can lead to misleading results. For example, if patients who receive a treatment tend to be sicker, we may incorrectly conclude that a treatment harms patients. Concerns over these biases have led several observational studies about Covid-19 treatments to be heavily criticized.
Do we need to wait for randomized trials to act? Not necessarily. The key lies in a set of tools economists have been using for decades: natural experiments.
With natural experiments, you can get around many of the hidden biases that plague observational studies by looking for circumstances that happen by chance — events that cause patients to be essentially randomized to one treatment or another. One study used a national shortage of the drug norepinephrine as a natural experiment to assess the drug’s effect on the mortality of patients critically ill with sepsis, comparing mortality rates of otherwise similar sepsis patients in the months before, during and after the shortage.
Although natural experiments are commonly used by economists, they’ve been infrequently used in medicine, where randomized trials have appropriately dominated.
Ashish Jha, recently appointed the dean of the Brown University School of Public Health, said that while “natural experiments have causal interpretations, typical associational studies in medicine do not, which may make some medical researchers less comfortable interpreting the results.”
But randomized trials may not always be available. Or they may be too cumbersome to perform, or not ethical. Most doctors can relate to recent comments by the Food and Drug Administration director Stephen Hahn in last week’s congressional pandemic hearing. “In a rapidly moving situation like we have now with Covid-19,” he said, decisions are made “based on the data that’s available to us at the time.”
So, until the trials arrive, here are some ideas for how natural experiments could help:
Timing of treatment
Patients hospitalized with critically ill Covid-19 infection in the days before the Recovery trial results were announced would be expected to have worse outcomes than otherwise similar patients hospitalized in the days afterward, assuming doctors suddenly started using more dexamethasone (which they almost certainly have). Consistent with the trial results, we would expect to see an effect only in Covid-19 patients who were critically ill.
Based on the trial’s results, it’s also reasonable to think that once patients are critically ill, earlier treatment with dexamethasone might lead to better outcomes (the steroid has not been shown to be effective with patients who are not on respiratory support). This hypothesis could be tested by evaluating whether mortality rates were lower for patients hospitalized with severe Covid-19 infection in the one to two days before the Recovery announcement compared with otherwise similar patients hospitalized in the week prior — who would, by chance, be getting the drug later in their disease course.
Staggered changes in protocols
Changes over time in practice patterns within hospitals could also be used to better estimate the effectiveness of Covid-19 treatments. Hospitals have varied considerably in their treatment protocols for Covid-19, and these protocols have changed in the months since the pandemic began. The staggered change in treatment patterns across hospitals could allow researchers to estimate the effectiveness of Covid-19 treatments by using each hospital, at a different period in time, as its own control.
For example, if dexamethasone is indeed effective, we would expect that hospitals that quickly incorporated the drug into treatment protocols after the Recovery trial announcement would experience earlier reductions in Covid-19 deaths than hospitals adopting it later. The key to this natural experiment would be to verify that the average characteristics of coronavirus patients within a hospital would be unchanged in the short interval before protocols were changed versus afterward.
Just above or below a threshold
The sometimes-arbitrary thresholds that hospitals use to decide which patients receive specific treatments could be used to better estimate the effectiveness of Covid-19 treatments. Treatment decisions often rely on clinical cutoffs, such that patients immediately above or below a threshold have very different likelihoods of treatment despite being otherwise similar.
For example, if a hospital decides that every person needing more than six liters per minute of oxygen will go on a ventilator, patients using six liters will go on a ventilator, but those using five liters will not — even though they are much the same.
The receipt of treatment is therefore effectively random for those patients near the cutoff, something economists call a regression discontinuity. To the extent that hospital protocols specify thresholds above or below which a scarce treatment can be given, knowledge of these thresholds could be used to demonstrate whether differences in treatment around the threshold correspond to differences in clinical outcomes.
These are just a few ideas to demonstrate the types of questions we could be asking to avoid the common biases encountered when using observational data. But it’s important to remember that natural experiments are happening by accident all the time, and many have already happened — it’s just a matter of looking for them. Randomized trials will remain the gold standard in health care, but just because these methods may be new to some health researchers does not mean we shouldn’t be using them when trials either take too long or cannot be done at all.
Anupam B. Jena, M.D., Ph.D., is an economist, a physician, and the Ruth L. Newhouse Associate Professor at Harvard Medical School. Follow him on Twitter at @AnupamBJena. Christopher M. Worsham, M.D., is a pulmonologist and critical care physician at Harvard Medical School. Follow him on Twitter at @ChrisWorsham.A version of this article appears in print on July 2, 2020, Section B, Page 6 of the New York edition with the headline: What Coronavirus Researchers Can Learn From Economists.
A series of tweets from a young psychiatry resident in the midst of the COVID-19 pandemic were stoic, straightforward, and heartbreaking.
“I’m a 30-year-old doctor. I was supposed to get married next month. I’m volunteering to treat patients with COVID-19 on the frontline,” tweeted Sofia Noori, MD, a third-year psychiatry resident at Yale School of Medicine, New Haven, Connecticut.
“My medicine friends needed help and I’m not going to let them down,” she continued. “I canceled my wedding. I wrote my will instead.”
Noori was a few days into a 2-week rotation, helping out on the COVID-19 unit at her hospital. Ironically, she said, she was more anxious before being redeployed than when she actually got there.
“When we found out that we could volunteer to help, I felt it was my duty to do so. It helped me find meaning in this whole crazy pandemic that we’re going through and actually calmed me down,” Noori told Medscape Medical News.
“It was nice to know that all of us, no matter how much we subspecialize, still have this core knowledge to help people with,” she added.
Noori is just one of many young psychiatrists who have volunteered at the front lines of the COVID-19 pandemic. Doing so, they say, has given them a new understanding of medicine — and of themselves.
Isobel Rosenthal, MD, “was at the very beginning” of her career as a psychiatry intern when her general medicine rotation became COVID-19 medicine at Mount Sinai Hospital in New York City, where she went through a 6-week rotation.
If there’s another wave of cases in the future, Rosenthal said she would volunteer to go back.
“I hadn’t [predicted] my career going into being a primary care provider during a pandemic, but I felt supported and empowered by my team. Although the experience was difficult, I signed up to be a physician and if there’s a need for me to go back, I would,” she told Medscape Medical News.
The Next Wave of Frontline Providers
According to Joshua Gordon, MD, director of the National Institute of Mental Health, “psychiatry residents particularly, but also psychiatrists across the board, are playing all kinds of roles in the hospital” during this time, including helping out in the ICU, the ED’s, and elsewhere.
“Especially when hospitals don’t allow visitors and doctors are overwhelmed, keeping patients’ families informed about conditions and needed discussions is something psychiatrists are really skilled at,” Gordon told Medscape Medical News.
“We have important roles to play directly in the COVID pandemic but we’re also going to be the next wave of frontline providers, dealing with the indirect yet significant effects of mitigation and economics and social distancing. That’s where we’re going to be needed and it’s going to be more and more important as the weeks wear on,” he said.
Emily Pinto Taylor, MD, chief resident, Yale Primary Care and Internal Medicine, supervised Noori’s volunteer group’s COVID-floor rotation. The psych residents “transitioned pretty seamlessly” into their new roles, she said.
“They had already been doing internal medicine boot camp courses online,” and one even took a course from the Society of Critical Care Medicine on COVID-19 ICU basics for non-intensivists, she noted.
“During COVID, all of the patients essentially have the same underlying medical problems. It tends to be variations on a theme, depending on what their other comorbidities are and how we treat them, but management is somewhat routine,” Pinto Taylor said.
However, because many of their patients had comorbid psychiatric illnesses, the residents’ expertise on treating conditions such as uncontrolled schizophrenia or delirium and confusion in elderly patients proved quite useful, she said.
“Having psych residents helped us think through how we could best manage their mental status and how to reorient people,” she said.
“Facing My Mortality”
Noori wrote her will right before redeployment. “I had to face my mortality because I knew there were healthcare workers who had passed away” after being on the COVID-19 front lines, she said.
Now that she’s a few weeks past her rotation, Noori looks back at her time volunteering as positive and meaningful, albeit challenging.
She was a primary care doctor on the COVID-19 unit, which could hold up to 30 patients. Many times the number of patients was near maximum capacity, while other times it was half to two thirds full. She ordered oxygen and medications as needed and developed treatment plans. Her 2-week volunteer group included four psychiatry residents, along with an attending and a chief resident.
“The last time I had had a medical rotation was about 2 years ago,” said Noori, who is now a senior resident. “Having more supervision was really helpful since I was so rusty, but it all came back quickly.”
Noori said that during her redeployment, she was surprised how many members of the same families were affected by the disease. There were multiple couples where, for example, the wife would be on the COVID-19 floor and the husband at a different unit or even location.
“We had to figure out how best to support them. Also, sometimes the families didn’t want us to tell a spouse that the other one was also hospitalized or had died because they were worried it would hasten the [first spouse’s] death,” Noori recounted.
She also recalled a patient who needed an increasing amount of oxygen, while the patient’s partner was sick in another hospital and another family member had died from COVID-19 complications. “It was really sad to see how many families had been devastated,” she said.
Throughout all of it, Noori said, her psychiatric training was useful. “Because we speak day in and day out with people and families about their emotions, we’re better equipped to have certain discussions in some ways. We were ready from the get-go for those difficult conversations.”
Staying Grateful
During her redeployment rotation in New York City, Rosenthal wrote an essay about her experiences, which was picked up by Katie Couric’s Wake-Up Call site.
“In it I wrote about going into the situation being stressed and scared, and those weren’t necessarily feelings that went away. Like many of my colleagues, I was living by myself during the time that I was taking care of patients because I was worried about infecting my boyfriend,” she said.
She also started a gratitude journal, “because I needed that motivation to keep my head in the game and wanting to come back and do my job.”
Like Noori, Rosenthal was assigned to a general-medicine team that took care of patients positive for COVID-19. The team was capped at about 14 patients, whose care was shared between two residents and an attending physician.
For the healthcare providers and patients alike, she said, it was an experience like no other. PPE severely limited patient contact and the doctor/patient-relationship building she was used to. The clinicians found themselves engaged in atypical tasks such as holding up iPads so patients could livestream with their families.
Although it was a difficult time, Rosenthal said there were also some good moments. At one point, a group of first responders stood outside her hospital and clapped in appreciation as frontline workers walked out. “It was such as amazing experience,” she said.
“I think being part of a larger team within the hospital is something that will change my perspective on the rest of my training,” she said. “It’s important that we all stay up to date with other parts of medicine, not just our specialties,” Rosenthal said.
“Great Privilege”
Surinder Moonga, MD, and Christian Romanchek, MD, are psychiatry residents at Johns Hopkins in Baltimore, Maryland, who also volunteered to redeploy to the ICU unit at their own hospital.
Although there wasn’t a big surge in COVID-19 cases during their rotations, the hospital wanted to pull in healthcare providers from different specialties to prepare them for what the future may bring.
Moonga had gone through about 7 weeks on the ICU floor during his intern year and understood there was a need to help out during the pandemic.
Most of the patients he saw were intubated, so communication was difficult. However, he was able to help manage patients’ agitation and “what we called ‘ICU delirium,’ ” Moonga said.
But it was when he was talking with patients’ families that his psychiatry training really kicked in.
“Families were suffering tremendously because they couldn’t be with their loved ones,” he said. “I provided therapy over the phone and reoriented their perspective on this really horrible thing that was happening to them. It was an honor to do this and I think it’s only going to help make me a better doctor,” he said.
Romanchek had completed an entire year in internal medicine before coming to Johns Hopkins, so he felt this experience would be helpful on the COVID-19 front lines. “Still, it’s been an adjustment transitioning back to medicine in a high-stakes setting,” he said.
He noted that other members of his team were incredibly supportive, and he had a lot of supervision. In addition, his institution provided educational materials about the coronavirus, as well as refresher information and videos on basic ICU and general critical care.
For other psychiatrists interested in doing what he did, Romancheck had some advice.
“I would say everything you can learn about acute respiratory distress syndrome would be helpful because that’s what we’re doing on the day-to-day,” Romanchek said. He added that reading about ongoing research into COVID-19 treatments is also essential.
Overall, “it’s been a really interesting experience for me and a really rewarding one,” he said.
Brave, Resilient
Noori said the pandemic helped her realize that “all of us are braver and more resilient” than they thought. “Also, this experience reminded me that I am a medical doctor and, when push comes to shove, I can care for people even if it’s not in my specialty.”
Although she would volunteer again if needed, Noori said it was a very personal decision. “At least for me, it’s actually really healing to know you did what you could do to help others during a time when it feels like everything is out of your control.”
Volunteering wasn’t without its challenges. She had a ritual she’d follow when she came home from the hospital each night, in which she would immediately put her clothes into a trash bag, shower, put the clothes into the laundry, and “not let anyone touch anything.”
“It took me 30 to 40 minutes every night to basically disinfect myself before I could pet my dog or kiss my fiancé,” she said.
Walking through the room during the interview, Noori’s fiancé said he knew volunteering was something she needed to do, “so I was all for it.” But when asked if he had been scared for her during that time, he quietly said, “Yeah, I was.”
Covid-19 news: Cases rising in Europe following eased lockdowns
Reporter: Gail S. Thornton, M.A.
The latest coronavirus news updated every day including coronavirus cases, the latest news, features and interviews from New Scientist and essential information about the covid-19 pandemic
A worker with the German Red Cross takes a throat swab sample from a local resident in the village of St. Vit following a Covid-19 outbreak at a nearby meat packaging centre
Latest coronavirus news as of 5 pm on 25 June
Coronavirus cases rising in Europe following eased lockdowns, says WHO
New cases of the coronavirus rose in Europe last week, for the first time in months. The increase was driven by 11 countries that have had a “very significant resurgence”, Hans Kluge, head of the World Health Organization Regional Office for Europe, said today. If left unchecked, such outbreaks will “push health systems to the brink once again”.
The countries and territories with notable increases in cases are Sweden, Armenia, Republic of Moldova, North Macedonia, Azerbaijan, Kazakhstan, Albania, Bosnia and Herzegovina, Kyrgyzstan, Ukraine, and Kosovo, according to a WHO spokesperson.
Kluge said there had also been outbreaks in Poland, Germany, Spain and Israel in schools, coal mines and food production settings, but authorities there had responded quickly. “Where new clusters of cases appeared, these have been controlled through rapid and targeted interventions,” said Kluge.
Germany, for instance, saw new daily cases rise from around 300 to over 600 last week, after an outbreak in a slaughterhouse. In response, the Guetersloh area reimposed lockdown conditions.
“There is no effective treatment yet and no effective vaccine yet, hence it’s so important we are not complacent,” said Kluge.
Other coronavirus news
Several US states have also seen increases in the number of new coronavirus cases. California, Florida and Texas, the three states with the biggest populations in the US, are seeing rising numbers of covid-19 infections, with several thousand new cases a day.
Fourteen doctors and researchers have said antibody testing for a past infection with coronavirus is uninformative and a waste of health care staff’s time, in a letter to the British Medical Journal. Hospitals in England were told to provide antibody testing four weeks ago, but a positive test result doesn’t mean someone is immune to the virus, so people still have to take the recommended safety precautions, the authors said.
Pregnant women in the US are more likely to develop severe covid-19, according to new figures from the US Centers for Disease Control and Prevention. The agency has found that 32 per cent of pregnant women with the virus were hospitalised, compared with 6 per cent of women in the same age group who were not pregnant.
The worldwide death toll has passed 483,000. The number of confirmed cases is more than 9.4 million, according to the map and dashboard from Johns Hopkins University, though the true number of cases will be much higher.
How to stop coronavirus deaths: We now know that the coronavirus kills by disrupting both our immune systems and blood clotting. But doctors are finding ways to beat this and boost survival rates.
Lasting symptoms: From extreme fatigue to weight loss, numbness, breathing difficulties and chest pain, some people’s covid-19 symptoms are proving very hard to shake.
Lung damage: Lung inflammation and blood clots caused by covid-19 can lead to scarring and long-term breathlessness and coughing in some people, for which there is no treatment.
UK health leaders warn there is a “real risk” of a second wave
A second wave of coronavirus infections in the UK is a “real risk” and all political parties should work together to ensure the country is ready for it, warned a group of health leaders including presidents of the Royal College of Physicians, Surgeons, GPs and Nursing and the chair of the British Medical Association. In a letter addressed to leaders of UK political parties published on the British Medical Journal’s website, they say, “the available evidence indicates that local flare-ups are increasingly likely and a second wave a real risk. Many elements of the infrastructure needed to contain the virus are beginning to be put in place, but substantial challenges remain.”
The letter calls for a “cross party commission” including all four nations of the UK, “that could rapidly produce practical recommendations for action.” They highlight several areas needing attention, including parliamentary scrutiny of national and local governance, procurement of goods and services, better public health coordination and the “disproportionate burden on black, Asian, and minority ethnic individuals and communities.”
In parliament today, Labour leader Keir Starmer asked UK prime minister Boris Johnson why the NHS Test and Trace system was only able to reach just over 10,000 people in England when Office for National Statistics figures estimated that 33,000 people were infected. Johnson said the Labour leader’s numbers were misleading, prompting an intervention from the Speaker Lindsay Hoyle, who asked Johnson to take back his comment.
Other coronavirus news
The UK government is not certain that the R number in England is below 1, according to leaked documents from Public Health England seen by Huffington Post UK. The document, dated last Thursday, says, “we cannot preclude [the R number] being above 1” and “there is some evidence that [the R number] has recently risen in all regions and we believe that this is likely to be due to increasing mobility and mixing between households.”
The European Union is considering blocking US visitors from travelling to EU nations. People in countries with severe outbreaks of coronavirus “where the virus is circulating most actively,” would not be allowed to enter, according to an EU diplomat quoted by CNN. The list of blocked nations could include the US, Brazil, Russia, Peru, Chile, Panama and Saudi Arabia.
People in Scotland will be able to meet indoors with up to two other households from 10 July, and pubs and restaurants will be allowed to re-open from 15 July.
Mothers with suspected or confirmed covid-19 should be encouraged to breastfeed as the “benefits of breastfeeding substantially outweigh the potential risks for transmission”, says a scientific briefing from the World Health Organization.
Coronavirus deaths
The worldwide death toll has passed 478,000. The number of confirmed cases is more than 9.2 million, according to the map and dashboard from Johns Hopkins University, though the true number of cases will be much higher.
The novel coronavirus seems able to infiltrate just about every inch of the human body, from the brain to the heart and lungs, into the gut, and right down to the toes, causing a dizzying array of symptoms ranging from annoying to fatal. It’s a list that doctors expect to grow even longer.
“It’s been unprecedented in many ways,” says Robert Salata, MD, a professor of medicine in epidemiology and international health at Ohio’s Case Western Reserve University. “In terms of the complications we’re seeing, it’s incredible.”
Covid-19 is among the most dangerous and intractable new viral diseases seen in years, perhaps decades. It “can attack almost anything in the body with devastating consequences,” says Harlan Krumholz, MD, a cardiologist at Yale New Haven Hospital. “Its ferocity is breathtaking and humbling.”
Severe cases often involve two phases, explains Mahalia Desruisseaux, MD, an associate professor of internal medicine focusing on infectious diseases at Yale University School of Medicine. As with the flu or other viral infections, Covid-19 typically subsides after several days, because the immune system mounts a response and neutralizes the virus, Desruisseaux says. But for some people, especially those over 65 and those with underlying health conditions and sometimes even in healthy adults and even children, a second phase kicks in.
Cells in key organs and entire body systems can become inflamed and damaged irreparably, and the risk of deadly blood clots skyrockets.
“The inflammatory response to the virus gets disproportionately exaggerated, triggering massive inflammation in several organs,” Desruisseaux says. “The flu-like viral illness seems to start to get better, and then boom, the overactive immune response just hits.”
Cells in key organs and entire body systems can become inflamed and damaged irreparably, and the risk of deadly blood clots skyrockets. “It’s our own immune system going haywire,” Salata tells Elemental.
Here are most of the known symptoms of Covid-19, followed below by deeper explanations for some of the strangest aspects of the disease.
Infographic by Elemental; Image source: LEONELLO CALVETTI/SCIENCE PHOTO LIBRARY/Getty Images
The strangest cases
The coronavirus infection begins mainly in the throat, and for many people, it may not go beyond that. But in some cases, the virus dives deep into the lungs, or the mucus-encased viruses can slide from the throat into the stomach. From there, it can spread elsewhere through the entire digestive system and into the bloodstream.
The lungs contain a large concentration of cells that have receptors for SARS-CoV-2, meaning the virus can easily gain entry to the cells, hijacking their genetic machinery in order to reproduce. This process damages or destroys lung cells and triggers the massive immune response, often leading to hospitalization.
But those same receptor cells exist in blood vessels, in the brain-blood barrier, in the intestines, and in nerve endings, possibly explaining why this coronavirus is able to wreak havoc in so many areas of the body.
Brain swelling and confusion
Fever and headaches can be signs of many illnesses, and they are symptoms of Covid-19, too. Some people have gone to health care facilities in states of confusion or disorientation, sometimes with headaches and fever, sometimes not, only to be diagnosed with Covid-19.
In one case study, brain scans revealed swelling on the brain of a Covid-19 patient, a condition known in other viral infections to cause altered mental status and seizures. One study of 214 Covid-19 patients found 36.4% had neurological symptoms, including dizziness, headaches, impaired consciousness, and seizures.
It’s not yet known if the coronavirus actually infects the brain or if the brain-related symptoms happen because the disease’s impact on the lungs also rob the brain of oxygen.“It is very difficult to separate the two,” says Chethan Rao, MD, a practicing physician and associate professor of neurology and neurosurgery at Baylor College of Medicine Medical Center.
Cytokine storm
When people infected with Covid-19 develop the classic symptom of breathing difficulty, it’s because the coronavirus has infected the lungs and the immune system is at work.
Most patients recover. But if the infection persists, the immune system goes into overdrive, releasing a flood of inflammatory proteins, called cytokines, that contribute to cell death and lead to acute respiratory distress syndrome.
When a cytokine storm strikes, lung tissue can become irreversibly scarred, the lungs fill with fluid, and patients often die. The flood of cytokines also fuels an overload of white blood cells, one of the body’s primary protectors which, in the confusion, begins to attack healthy cells, according to a May 13 study in the journal Frontiers in Public Health. This overaction by the immune system causes hyperinflammation in tissues that can also affect other parts of the body by causing leaky blood vessels, extremely low blood pressure, and a lack of oxygen in the blood.
Silent hypoxia and Covid pneumonia
Some people with Covid-19 develop dangerously low levels of oxygen in their blood but otherwise don’t feel terribly sick. They might complain of mild flu-like symptoms and perhaps a little shortness of breath or maybe just tiredness.
The condition has been called silent hypoxia and resembles the low oxygen levels a person suffers when breathing the thin air at high altitudes. These people are in critical condition, though they don’t realize it. (X-rays reveal their air sacs in the lungs are filled with fluid or pus.) The low oxygen levels, untreated, can quickly cascade into serious breathing problems and damage to other organs.
Scientists don’t know exactly what’s going on, but some doctors are calling the condition Covid pneumonia. Autopsies of a small number of people who died from Covid-19 find, because of all the water, lungs weighing more than four pounds, and in one case seven and a half pounds, compared to the normal average of under two pounds.
Blood clots
Only recently have doctors realized that Covid-19 seems to be infecting blood and damaging blood vessels. In one study, 31% of people in intensive care with Covid pneumonia had blood clots. These clots, which the body creates in an effort to stop bleeding, can break up and travel to the lungs or cut off blood flow to the brain, causing a stroke.
“Blood thinners don’t reliably prevent clotting in people with Covid-19, and young people are dying of strokes caused by the blockages in the brain,” science writer Cassandra Willyard notes in a review of the early research on the topic for the journal Nature.
The presence of blood clots can be indicated by levels of protein fragments from the clot, called D-dimer. Doctors are seeing unusually high D-dimer levels in many Covid-19 patients.
“We’ve never seen such high levels before,” says Salata, the Case Western physician. One woman recently had levels that were “just not heard of before,” he said. He and his colleagues are finding major clots as well as unusual numbers of smaller clots that can damage the heart, lungs, kidneys, and other organs.
Inflammatory syndrome in children
In late April and early May, a mysterious toxic shock syndrome began showing up in children in various countries, causing at least three deaths in New York. Some cases have been firmly tied to Covid-19 diagnoses; others have not.
The symptoms of pediatric multisystem inflammatory syndrome, as it’s being called, resemble an unrelated syndrome called Kawasaki disease, a leading cause of heart disease in children. Both are marked by high fever, rash, cracked lips, and bloodshot eyes.
It’s not clear yet if Covid-19 and Kawasaki disease are perhaps occurring simultaneously, but Salata thinks the new cases are probably yet another severe immune-system reaction to Covid-19 that only looks like Kawasaki disease. “We don’t know for sure,” Salata says, “but that’s what it really looks like.”
Loss of smell and taste
The loss of smell, called anosmia, can be caused by the common cold, when congestion mucks up nose and nasal passages. Other diseases can trigger anosmia by disrupting or killing the olfactory nerves high in the nasal cavity.
But doctors were surprised earlier this year when people with anosmia and no other symptoms, or only mild symptoms, tested positive for Covid-19. It’s not yet certain how Covid-19 triggers anosmia, but remember those receptor cells that readily receive the coronavirus, present in the lungs and elsewhere? Similar cells exist in the olfactory epithelium, a layer of skin containing the neurons that detect scents.
Covid toes
Yet another bizarre symptom of Covid-19 is ischemia of the fingers and toes, a reduction of blood flow that causes red or purplish lesions at the ends of the digits. Dubbed Covid toes, the condition can be painful and, if left untreated, can lead to tissue death. It’s showing up mostly but not exclusively in younger people, who sometimes have few other symptoms or none.
Like anosmia, Covid toe tends to heal without long-term complications, but both can be signs that someone has Covid-19 and is infectious, even if they feel no other symptoms.
Like many other complications of Covid-19, researchers have barely had time to study the reasons beyond this symptom, but one analysis, published April 15 in The Lancet, suggests it’s due to reduced function in small blood vessels.
What’s next?
Covid-19 is not alone among germs in generating a range of mild to serious outcomes.
“Viruses are so weird,” says Yonatan Grad, MD, an assistant professor of immunology and infectious diseases at Harvard T.H. Chan School of Public Health. Grad doesn’t mean to discount the devastating effects viruses can have, but he says they can bring “all sorts of unusual manifestations.”
The herpes virus causes unsightly cold sores, for example, but can also prompt a deadly swelling of the brain. The poliovirus generates no visible symptoms in most people while about 1 in 200 ends up with parts of their bodies paralyzed.
Meanwhile, Covid-19 likely has more surprises in store.
“We don’t know everything about this virus,” Salata says. “So stay tuned. I’m not sure we’ve seen it all yet.”
The following article is reprinted by the American Heart Association News.
Reporter: Gail S. Thornton, M.A.
Dr. Tomisaku Kawasaki at the 11th International Kawasaki Disease Symposium in 2015. He died last week at age 95.Pediatrician Dr. Tomisaku Kawasaki early in his career. (American Heart Association Archives)
In the early 1960s, pediatrician Dr. Tomisaku Kawasaki saw more and more children suffering from persistent fevers, bumpy rashes and more unsightly, uncomfortable symptoms. So he began stashing their records in a special file. He labeled it with the Japanese equivalent of “GOK.”
“GOK,” he later told English-speaking friends, “stood for ‘God Only Knows.'”
Once he had 50 cases, Kawasaki published a study announcing the discovery of an inflammatory disease. The scientific name he gave didn’t stick. It instead became known as Kawasaki disease, which has been in the news recently for a possible connection to complications of COVID-19.
The publication of his findings launched Kawasaki from unknown outsider to a giant in his field. Yet he remained humble, fun-loving and – most of all – devoted to treating and understanding the disease. He died June 5 in Japan, the Kawasaki Disease Research Center announced Wednesday. He was 95.
“He lived a wonderful life, he made incredible contributions and he was quite the character – the life of every party,” said Dr. Jane Newburger, director of the Kawasaki Program and professor of pediatrics at Harvard Medical School in Boston. “Even when he was well past the time of doing research himself, he very much pushed the research agenda, and he remained intellectually curious into his 90s. He was an iconic figure and a remarkable person.”
Discovering a disease is a career-defining feat, the scientific version of being crowned boxing’s undisputed heavyweight champion. It’s an apt comparison because there’s a “Rocky” quality to Kawasaki’s tale.
He wasn’t an academic scientist; he was a workaday pediatrician. He didn’t have a lab at a prestigious institution; he saw kids at the Japan Red Cross Hospital in Tokyo. He was keenly aware of these things, which is why he waited until he had 50 cases before being so bold as to proclaim his discovery. In further deference to his outsider status, he published his groundbreaking science in a lesser-known allergy journal – even though allergies have nothing to do with Kawasaki disease.
“He was an outsider in the intense hierarchy of Japanese academic medicine and his discovery was not embraced by some members of the medical establishment,” said Dr. Jane Burns, director of the Kawasaki Disease Research Center at the University of California San Diego, a translator of his landmark study and a creator of a documentary about the disease. “However, he went on to rock-star status on the global stage. His generous nature made him accessible to pediatricians throughout the world.”
Added Newburger: “He had to defend his new observations against many skeptics in the academic community. That was quite courageous.”
Kawasaki disease is marked by a fever that lasts at least five days and multiple other symptoms from a list that includes an extensive rash, bloodshot eyes, cracked lips, strawberry tongue, swollen lymph nodes in the neck, reddened palms and/or soles, and swollen hands and/or feet.
Most patients are 5 or younger, with the average age around 2, although some are as old as teenagers. Boys are more likely to have it than girls. While it’s seen in all races and ethnicities, the genetic pattern that makes a child susceptible is most prevalent in children of Asian descent.
In the United States, there are about 5,440 Kawasaki disease hospitalizations per year, according to the Centers for Disease Control and Prevention. A new case is diagnosed on average every week at Lurie Children’s Hospital in Chicago, said Dr. Stan Shulman, who leads the Center for Kawasaki Disease at Lurie Children’s and Northwestern University Feinberg School of Medicine. He also is professor of pediatric infectious disease at Northwestern.
From left: Dr. Stan Shulman, Dr. Tomisaku Kawasaki and Dr. Anne Rowley. (Photo courtesy of Dr. Stan Shulman)
Kawasaki published his breakthrough paper in 1967 in Japanese. The English version appeared in 1974. By then, the disease was linked to heart problems, adding to the urgency for more research. Effective treatments arrived in the 1980s. The current treatment plan includes intravenous immunoglobulin plus aspirin.
“Before the modern therapies, about 25% of children with Kawasaki disease developed heart disease. Now, it’s about 2% to 4%,” Shulman said. “That’s essentially a 90% reduction.”
Kawasaki’s initial paper was incredibly thorough: 53 pages with handwritten drawings detailing each patient’s rash, Burns said. She called the document “probably one of the most beautiful examples of descriptive clinical writing.”
He initially didn’t suspect a connection to heart disease. Further research pinpointed that Kawasaki disease causes inflammation of the blood vessels, particularly in the heart. That’s why the disease recently was connected to COVID-19.
Some children with COVID-19 developed multisystem inflammatory syndrome. That syndrome often was described as a “Kawasaki-like illness.” Shulman said the relationship is “somewhat debatable.”
“Although some of the patients have some signs of Kawasaki disease, there are quite a few striking differences as well,” he said. “We’re still trying to sort out what it all means.”
Many important questions about Kawasaki disease remain unanswered, including important issues such as what triggers it and why the most effective treatments are so effective. There’s also no specific test for it; diagnosis is based on clinical signs and symptoms with some help from non-specific laboratory tests.
The hunt to solve those mysteries sustains a worldwide network of scientists focused on the disease.
Since 1984, the American Heart Association has co-sponsored the International Kawasaki Disease Symposium; it’s held every three years. In 1987, the AHA changed the name of its longstanding Rheumatic Fever and Infective Endocarditis Committee to include Kawasaki Disease; Shulman was the chairman of the committee at the time. Newburger later chaired the committee.
While scientists often take deep dives into a disease, it’s rare for them to meet – much less befriend – the person who discovered that disease. Yet for the past 50 years, a perk of studying this disease was spending time with Kawasaki, a regular at the symposium and frequent lecturer around the world.
Kawasaki thrived as the center of attention. Long before cellphones and selfies, he loved taking pictures with everyone at a meeting. He personally plotted the opening and closing ceremonies of the symposiums, and the crescendo of every party was him offering the Japanese toast, “Kampai!”
“There really was a cult, almost, around Dr. Kawasaki because he was so incredibly warm and engaging,” Newburger said. “His combination of intellectual rigor and wonderful social skills made him so beloved.”
Dr. Tomisaku Kawasaki. (Photo courtesy of Kathryn Taubert)
Those dual traits clicked at the inaugural symposium when Kawasaki realized the gulf between the English speakers and Japanese speakers. He made sure future gatherings had real-time translators.
“That’s how the Kawasaki disease scholars in Japan and the United States came to know each other very well,” Newburger said. “Those international relationships are part of his marvelous legacy.”
Kawasaki visited Chicago three times over 20 years, the last in 2005. On one trip, Kawasaki was feted as such a celebrity that Shulman told the Chicago Sun-Times that “being around Dr. Kawasaki was like traveling with a rock star.” The phrase made it into the headline, much to Kawasaki’s delight.
On another visit, Kawasaki wanted to attend a Chicago Bears game. Alas, they were out of town. So the Shulmans took Kawasaki and his wife, Reiko, to a game at the University of Wisconsin, where Shulman’s daughter was a student.
“They had weekly showings of NFL games on TV in Japan, so he really was a football fan,” Shulman said. “But what he enjoyed most was the University of Wisconsin Marching Band performing what they call the Fifth Quarter. After the game, the band comes out and marches around the field in what looks like absolute chaos but of course is very organized. Coming from the rigid Japanese culture, the Kawasakis just ate it up. He never stopped talking about the Fifth Quarter.”
Kawasaki was born in 1925 in Tokyo, the youngest of seven children, according to a 2007 profile in The Japan Times. He was fascinated by how plants and fruits grew, but he followed the path his mother wanted and became a doctor.
As an intern working soon after World War II, he found that “adult patients were full of complaints, but sick children said little,” he told the newspaper. So he went into pediatrics.
He landed a job at the Red Cross Hospital in the Hiroo neighborhood of Tokyo. In 1961, he saw a 4-year-old boy with “this unusual sickness for which I could find no reference in any medical literature.” A colleague dismissed it as a form of scarlet fever, but Kawasaki thought otherwise.
A year later, Kawasaki saw a similar illness in a child again and “realized that I had seen two instances which did not exist in any medical textbook.” The GOK file started to grow. When he wrote about the cases, Kawasaki called the condition “mucocutaneous lymph node syndrome.”
He stayed at the Hiroo hospital for 40 years until retiring. He established the Japan Kawasaki Disease Research Center and served as its director for many years; he remained its honorary chairman.
Over the years, he received many awards, including the first Japanese Pediatric Society Prize. He also received the ultimate acknowledgment of his importance within his nation’s embrace: an invitation to the Imperial Palace to discuss his work with the Emperor and Empress of Japan.
A funeral already has been held. The Japan Kawasaki Disease Research Foundation said it will soon announce plans for a memorial service. Also, the next International Kawasaki Disease Symposium is scheduled to be held in Tokyo in October 2021, providing another opportunity to celebrate Kawasaki’s life and legacy.
His wife died last year. No other survivor information was immediately available.
Oluwaseun Johnson-Akeju, MD, the newly-appointed Anesthetist-in-Chief at Mass General, shares his perspective on how his team is caring for the most critically ill patients on the frontlines of the COVID-19 crisis.
I began my tenure as chair of the department on Jan. 1, 2020, right before the onset of the pandemic. Many of our staff members have risen to the challenge of taking great care of critically ill patients that have been diagnosed with COVID-19. What I admire most is how our nurse anesthetists, residents, fellows, engineers, technicians and staff have rallied together, and, above personal concerns, demonstrated selfless service and personal courage to take care of our patients, and indeed humanity. I am very thankful and proud to lead our department.
Oluwaseun Johnson-Akeju, MD
How have the hospital’s pre-COVID-19 efforts to improve care for critically ill patients positioned you to better respond to this crisis?
We are fortunate to stand on the shoulders of giants who came before us. In 1961 Henning Pontoppidan, MD, started the first intensive care unit (ICU) at Mass General. This unit became the model for the entire country. A lot of the research that laid out the fundamental principles of anesthetic management of respiratory failures – such as the COVID-19-associated acute respiratory distress syndrome (ARDS) – came out of this ICU. Also, sentinel studies performed by Warren Zapol, MD, emeritus anesthetist-in-chief, laid the groundwork for the use of extracorporeal membrane oxygenation in ARDS. The rich critical care medicine pedigree of our department is evident in our master intensivists and our fellowship training program and has been leveraged for the treatment of COVID-19.
Our orders, if you will, are to protect our staff, steward scarce personal protective equipment resources, and to win the COVID-19 battle by providing the highest level of care to all patients.
How is your team addressing the challenges faced by patients who have been on a ventilator for an extended time?
Four key concerns come to mind. First, we need to keep our patients immobilized to tolerate the breathing tube and ventilation strategies that are essential for the lungs to heal. This makes it difficult to diagnose acute neurological complications, such as stroke. Second, in some instances, the long-term use of breathing tubes is associated with hoarseness and other manifestations of damage to the airway. Third, as you can imagine, immobilization for long periods is associated with muscle wasting and weakness. Finally, the aftereffects of our treatment strategies and COVID-19 infection are unclear. Fortunately, Lorenzo Berra, MD, and others in the department are working on national and international registries that would enable a better understanding of the epidemiology of COVID-19 infection and treatment.
What are some lessons learned that will continue beyond this pandemic?
All our Mass General departments worked collaboratively during this pandemic. Two examples stand out. First, to lessen the clinical load on our ICU physicians and nurses, a team from the departments of surgery, anesthesia and radiology formed the COVID-19 Bundled Response for Access team. This team established a safe, streamlined approach to perform vascular and enteral access procedures — such as placing arterial lines and feeding tubes — in critically ill patients diagnosed with COVID-19. Second, we significantly increased our ICU capacity by forming collaborations with various hospital teams to staff newly formed ICUs. I expect that continued collaborations will enable us to administer the highest quality of critical care to our patients by leveraging the clinical, scientific and educational perspectives that are unique to the various specialties that provide critical care at Mass General.
SARS-CoV-2 Testing and Outcomes in the First 30 Days After the First Case of COVID-19 at an Australian Children’s Hospital
Reporter: Gail S. Thornton, M.A.
2020
Objective: International studies describing COVID-19 in children have shown low proportions of paediatric cases and generally a mild clinical course. We aimed to present early data on children tested for SARS-CoV-2 at a large Australian tertiary children’s hospital according to the state health department guidelines, which varied over time.
Methods: We conducted a retrospective cohort study at The Royal Children’s Hospital, Melbourne, Australia. It included all paediatric patients (aged 0-18 years) who presented to the Emergency Department (ED) or the Respiratory Infection Clinic (RIC) and were tested for SARS-CoV-2. The 30-day study period commenced after the first confirmed positive case was detected at the hospital on 21st March 2020, until 19th April 2020. We recorded epidemiological and clinical data.
Results: There were 433 patients in whom SARS-CoV-2 testing was performed in ED (331 (76%)) or RIC (102 (24%)). There were 4 (0.9%) who had positive SARS-CoV-2 detected, none of whom were admitted to hospital or developed severe disease. Of these SARS-CoV-2 positive patients, 1/4 (25%) had a comorbidity, which was asthma. Of the SARS-CoV-2 negative patients, 196/429 (46%) had comorbidities. Risk factors for COVID-19 were identified in 4/4 SARS-CoV-2 positive patients and 47/429 (11%) SARS-CoV-2 negative patients.
Conclusions: Our study identified a very low rate of SARS-CoV-2 positive cases in children presenting to a tertiary ED or RIC, none of whom were admitted to hospital. A high proportion of patients who were SARS-CoV-2 negative had comorbidities.
From a physician who is completing his/her internship in NYC and working on the frontlines: I thought the ED was bad. And it seems to be getting a lot of attention, rightfully so. But if only people knew what’s happening behind the closed hospital doors, where pt’s can’t visit.
COVID19 Physicians
@Covid19Docs
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Inpatient medicine feels so dystopian. Overhead pages every 30 min, the codes are so frequent and numerous that you tune them out, only to be reminded by the buzzing pager. Within 30 min of starting my shift Wednesday, I found myself pushing into a dead person’s chest for 5
minutes, they called it, and everyone emptied out of the room. The body left lying there, connected to tubes, lifeless. Rushing to a code and then hearing another code called in route, not knowing which one to go to. Walking into the room thinking, “not again” and seeing people
pushing into lifeless bodies. Residents, attendings, and nurses who are detached and overtaken by the inevitable sense of defeat. Watching nurses anxiously and tearfully plead for direction from you as another patient starts crashing. You can see it in the nurse’s eyes…
that realization that it’s futile. That look of being forced to sit with feelings of helplessness. Another body piled into refrigerated semi-trucks. Yesterday morning, while I was rounding on my own patients, I discovered 2 dead patients. They were lying there cold, pulseless,
unresponsive. They died alone and no one had seen them for hours until I discovered them in the morning. It’s just so bizarre. It’s hard to believe this is real. And the way the residents are treated by the medicine department is so ****ty. As if they’re throwing us in to be
sacrificed. The floors are basically resident run now. Any attending over 50 is off floors. We round by ourselves, expose ourselves, and FaceTime our attending who never even sees the patients. Meanwhile the vice chair came in today to give us lip service. “You’re not alone”
despite being just that. “We’re listening” despite ignoring and minimizing concerns about PPE and poor infection control guidelines. Self-congratulating about how people wanna stay at the hospital after graduating.
It seems even the emails are crafted by lawyers now. They know what they’re doing and they know what they’re guilty of. It’s clear our role shifts between trainees and employees whenever it’s convenient for the hospital as we are exploited by people who sit comfortably in offices and homes, sitting on fat paychecks, not having to touch a single patient or deal with any of this.
COVID19 Physicians
@Covid19Docs
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pushing into lifeless bodies. Residents, attendings, and nurses who are detached and overtaken by the inevitable sense of defeat.
COVID19 Physicians
COVID19 Physicians
@Covid19Docs
·
that realization that it’s futile. That look of being forced to sit with feelings of helplessness. Another body piled into refrigerated semi-trucks. Yesterday morning, while I was rounding on my own patients, I discovered 2 dead patients. They were lying there cold, pulseless,
despite being just that. “We’re listening” despite ignoring and minimizing concerns about PPE and poor infection control guidelines. Self-congratulating about how people wanna stay at the hospital after graduating.
2
22
273
COVID19 Physicians
@Covid19Docs
·
It seems even the emails are crafted by lawyers now. They know what they’re doing and they know what they’re guilty of. It’s clear our role shifts between trainees and employees whenever it’s convenient for the hospital as we are exploited by people who sit comfortably in offices
I don’t usually rant on social media. However, after a week of service in the ICU, I’d like to get a few things off my chest. #COVID19 (1/10)
1) This is a horrible, relentless, nasty disease in its severe form. If the patient is obese and/or has renal failure, the prognosis is extremely grim. They are NOT dying from comorbidities. They are dying from COVID -19. #COVID19 (2/10)
2) When I say relentless; most patients make some improvements initially (days 4-6), but decompensate with a 2nd cytokine storm (as many have described). It is this 2nd decompensation that is deadly and that we need to prevent.
3) We are forced to share dialysis circuits given the high percentage of renal failure (these people had normal kidneys before!) Why isn’t there more press for this fact? We need more machines to manage our patients effectively. @NYTHealth@WSJhealth#COVID19 (4/10)
4) This IS ARDS full stop. While certain pts may be phenotypically different and benefit from lower PEEP, others de recruit quickly. Different phenotypes should be treated as such. We are seeing more atypical presentations than usual because the volume is tremendous. (5/10)
5) My interest is in thrombosis and there is a definite hypercoagulable state associated with this illness. Anticoagulation is all over the place at different centers, but there is no randomized data yet to guide any of it (working on it) #COVID19
6) Every single ICU patient (barring QTc issues) got hydroxychloroquine and it doesn’t seem to have helped. Maybe it helps for prophylaxis or in mild disease, but doesn’t appear to do anything once in ICU. It is NOT a pancea and should not be given indiscriminately. (7/10)
8) Be skeptical, but armchair conspiracy theories without any viable solutions are extremely disheartening. We are all in this together, help us generate the data that will answer those questions you are skeptical about and more importantly help our patients #COVID19 (9/10)
9) The rapid dissemination of materials, protocols, data is truly impressive. I feel like every intellect is pointed at one problem. Further, the support from people inside and outside of the hospital is truly overwhelming and much appreciated #COVID19@nyphospital (10/10)
I have only glimpsed what this disease can do, so hats off to the leadership for their transparency and stewardship over the last 6 weeks. It is remarkable to witness the level of dedication of each individual trying to make a difference. @nyphospital@ColumbiaMed
I alluded to it but felt remiss that I didn’t specifically mention that the nurses, residents, and fellows are truly superstars working tirelessly under less than ideal conditions #NYPHeroes
10) As was pointed out to me – PAs, NPs, housekeeping, food service, techs, CNAs, CRNAs, transport, security, parking, etc. They all contribute far more than most of us (including myself) and deserve our gratitude. #NYPHeroes
Yes course. Respiratory therapists. PT OT – I dont mean to exclude anyone. If I do – please forgive the mistake!
3/29/2020
Am I Part of the Cure or Am I Part of the Disease? Keeping Coronavirus Out When a Doctor Comes Home
Last year, after a month of dry cough and shortness of breath while walking up the steep steps of Fillmore Street in San Francisco, Mary, my mother-in-law and housemate, noticed that she was becoming more and more easily winded. When her symptoms didn’t improve over the next several weeks, her doctors at the University of California, San Francisco, ordered a CT scan. They found bronchiolitis obliterans, a chronic, progressive lung condition that leads to gradually worsening lung disease and respiratory collapse. There is no treatment for this disease, whose natural history ends in lung transplantation for patients who are young and healthy enough to undergo it. Mary has spent every day of the past year and a half focused on respiratory physiotherapy, practicing breathing techniques that ease her symptoms but do little to slow disease progression.
“What can Mama do to stay safe?” my wife asks, in light of the coronavirus cases now cropping up in San Francisco. There are many things we don’t yet know about Covid-19. We do know, however, that like many viral illnesses, it is most deadly to people who are elderly, already ill, or immunocompromised. And it is especially dangerous to those with lung conditions, given the predominance of pulmonary complications. I recommend the guidelines from the Centers for Disease Control and Prevention, telling my wife, “She can stay home, cover her coughs, and practice good hand hygiene.”1
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