Leaders in US, Europe divided on response to surging virus

Virus cases are surging across Europe and many U.S. states, but responses by leaders are miles apart, with officials in Ireland, France and elsewhere imposing curfews and restricting gatherings even as some U.S. governors resist mask mandates or more aggressive measures.

The stark contrasts in efforts to contain infections come as outbreaks on both sides of the Atlantic raise similar alarms, including shrinking availability of hospital beds and rising deaths.

Governors of states including Tennessee, Oklahoma, Nebraska and North Dakota are all facing calls from doctors and public health officials to require masks.

In Utah, a spike in cases since school reopened has created a dynamic that Republican Gov. Gary Herbert has called “unsustainable.”

But schools remain open and Herbert, who has been pressured by an outspoken contingent of residents opposed to masks, has resisted a statewide mandate. Instead, he announced last week that they would be required only in six counties with the highest infection rates, while leaving it to others to make their own rules. Meanwhile, many hospitals are being pushed to the breaking point.

“We are not just managing COVID. We are also managing heart attacks and strokes and respiratory failure and all those other things that need ICU-level care,” said Dr. Kencee Graves, chief medical officer for inpatient care at the University of Utah Health hospital in Salt Lake City. The hospital’s intensive care unit was filled by the end of last week, forcing the reopening of a backup intensive care unit.

“The sooner we take care of each other, wear masks, physically distance, the sooner we can have some gatherings in a safe way,” Graves said.

In Oklahoma, where the number of people hospitalized for the virus has reached record levels, doctors have called on officials to do more.

“We need face mask mandates to protect more of our Oklahoma citizens,” Dr. George Monks, the president of the Oklahoma State Medical Association, said in a tweet Sunday.

But Gov. Kevin Stitt has said repeatedly he has no plans to do so, citing concerns about how such a mandate would be enforced.

Oklahoma health officials reported a record high of 821 people hospitalized Tuesday with the virus or under investigation for the infection. Wyoming also reported a record high number of patients hospitalized for the virus.

New virus cases in the U.S. have surged in recent weeks from a daily average of about 42,000 in early October to about 58,000—the highest level since late July, according to Johns Hopkins University.

In one of the most troubling outbreaks, 10 residents of a nursing home in northwest Kansas have died from the virus, health officials said. All 62 residents of the Andbe Home in Norton County, as well as an unspecified number of employees, have tested positive for the infection.

The surge in new cases prompted a change of heart Monday from the mayor of North Dakota’s largest city, in favor of a mask mandate.

Tim Mahoney, who in addition to being Fargo’s mayor is also a general surgeon, has been largely supportive of Republican Gov. Doug Burgum’s approach of leaving management of the virus to local officials.

Mahoney, himself, cast the deciding vote against a mask mandate at a recent meeting of city officials. But with North Dakota leading the nation in new cases and up to one in four city residents now testing positive, Mahoney said a statewide change is in order.

The dynamic contrasts sharply with Europe, where national officials are battling a similar spike with measures including new lockdowns and smart phone apps that track the virus’ spread.

In Ireland, Prime Minister Micheal Martin announced a lockdown starting at midnight Wednesday that will close all non-essential stores, limit restaurants to carryout service and require people to stay within three miles (five kilometers) of their homes, while banning visits to other households.

It marks a near-return to restrictions imposed by the government in March, although schools, construction sites and manufacturing industries will remain open. If people comply with the restrictions, which will be in place until Dec. 1, the country will be able to celebrate Christmas “in a meaningful way,” Martin said.

But as cases surge, some decisions by European leaders to impose new restrictions are facing stiff opposition at the local level. After a tense faceoff, Britain’s government said Tuesday it had failed to reach agreement with Greater Manchester Mayor Andy Burnham, who has rejected tough new measures without money to support the workers and businesses that will be most affected.


Britain’s Communities Secretary Robert Jenrick expressed disappointment with Burnham, saying the mayor “has been unwilling to take the action that is required to get the spread of the virus under control.” Prime Minister Boris Johnson said Tuesday he would impose the restrictions, drawing criticism from Burnham.

“It cannot be right to close people’s place of work, to shut somebody’s business, without giving them proper support,” Burnham said. He said Manchester had sought 90 million pounds ($117 million) from the national government to help people get through the winter. It was unclear how much the city would receive.

In the Netherlands, which has one of the highest infection rates in Europe, a judge in The Hague rejected an appeal by more than 60 Dutch bars and restaurants to overturn a government four-week closure order.

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Criteria to predict cytokine storm in COVID-19 patients identified

Like a cold front that moves in, setting the stage for severe weather, coronavirus infection triggers showers of infection-fighting immune molecules—showers that sometimes escalate into a chaotic immune response known as a cytokine storm. About 20 to 30 percent of patients hospitalized with COVID-19 develop severe immune manifestations, in some instances leading to cytokine storm, with life-threatening organ damage and high risk of death.

Predicting which COVID-19 patients will develop cytokine storm is challenging, owing to the many variables that influence immune function. But now, in breakthrough work, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) have developed and validated predictive criteria for early identification of COVID-19 patients who are developing hyperimmune responses, raising the possibility for early therapeutic intervention.

“If we can anticipate cytokine storm, we can apply treatment sooner and possibly decrease mortality,” explained Roberto Caricchio, MD, Chief of the Section of Rheumatology, Director of the Temple Lupus Program, Professor of Medicine and Microbiology and Immunology at LKSOM, and lead author on the new report.

The report, published online in the Annals of the Rheumatic Diseases, is the first to identify criteria that can be readily used in clinical practice to potentially head off the worst of the hyperimmune attack against COVID-19.

The breakthrough is the result of an extensive collaboration between researchers and clinicians across multiple departments in the Lewis Katz School of Medicine and Temple University Hospital, constituting the Temple University COVID-19 Research Group.

According to Dr. Caricchio, large numbers of COVID-19 patients have been treated at Temple since the pandemic emerged in the United States. “We have a significant amount of data in terms of variables to predict cytokine storm,” he said.

Since early March, every patient admitted to Temple University Hospital (TUH) has had data on more than 60 different laboratory variables collected daily until the time of recovery or time of death. Among variables measured every day are factors like white blood cell count, metabolic enzyme activity, and markers of inflammation and respiratory function. Importantly these markers are commonly used in hospitals across the globe and therefore are readily available.

The research group carried out statistical analyses on laboratory data for 513 COVID-19 patients hospitalized at TUH in March and April, 64 of whom developed cytokine storm. A genetic algorithm was used to identify cut-off values for each individual laboratory variable to define the predictive requirements for cytokine storm. Genetic algorithms mimic the processes of natural selection and evolution in analyzing the data, and in this case, over multiple iterations, the algorithm turned up variables indicating which patients are most likely to develop cytokine storm.

Overall, the analyses yielded six predictive criteria comprising three clusters of laboratory results relating to inflammation, cell death and tissue damage, and electrolyte imbalance. In particular, patients in cytokine storm exhibited a proinflammatory status and elevated levels of enzymes indicating significant systemic tissue damage. Moreover, patients who met the criteria had extended hospital stays and were at increased risk of death from COVID-19, with almost half of patients who experienced cytokine storm meeting all criteria within the first day of hospitalization.

The researchers validated the criteria in a subsequent cohort of 258 patients admitted to TUH for COVID-19 infection. “The algorithm correctly predicted cytokine storm in almost 70 percent of patients,” Dr. Caricchio said.

“The ability to reproduce our results in a second cohort of patients means that our group of variables are effective criteria for cytokine storm diagnosis in COVID-19 patients,” he added. The final step now is to have the criteria validated by other centers where COVID-19 patients are admitted for care.

Dr. Caricchio noted that the criteria could be applied to COVID-19 patients at any hospital or level of hospitalization anywhere in the world. “This makes the criteria very valuable for guiding decisions about how to treat COVID-19 patients worldwide,” he said. Applied more broadly, the criteria could greatly facilitate early diagnosis and intervention, helping save many lives.

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Frere Jacques, are you sleeping? Research shows lullabies in any language relax babies

Virtually all new parents quickly discover that a lullaby will in fact help an infant unwind, but they might surprised to learn that babies aren’t fussy about the language.

Researchers at Harvard’s Music Lab have determined that American infants relaxed when played lullabies that were unfamiliar and in a foreign language. Their results were published in Nature Human Behaviour Oct. 19.

“There’s a longstanding debate about how music affects listeners as a result of both prior experiences with music and the basic design of our psychology,” said Samuel Mehr, a Department of Psychology Research Associate and Principal Investigator at the Music Lab. “Common sense tells us that infants find the lullabies they hear relaxing. Is this just because they’ve experienced their parents’ singing before and know it means they’re safe and secure? Or is there also something universal about lullabies that produces these effects, independently of experience?”

The new findings supported the latter hypothesis: Infants responded to universal elements of songs, despite the unfamiliarity of their melodies and words, and relaxed. The study was conducted in 2018 and 2019 at the Music Lab, which focuses on the psychology of music from infancy to adulthood.

In the experiment, each infant watched an animated video of two characters singing either a lullaby or a non-lullaby. To measure the infants’ relaxation responses to the recordings, the researchers focused on pupil dilation, heart rate changes, electrodermal (a measure of “arousal” or excitement, from electrical resistance of the skin), frequency of blinking, and gaze direction as indicators of relaxation or agitation. Generally, the infants experienced a decrease in heart rate and pupil dilation, and attenuated electrodermal activity in response to the unfamiliar lullabies.

The researchers had to act quickly because of the limited attention spans of their subjects; most babies could pay attention for about five minutes before getting distracted.

“In an ideal world, we would play babies a dozen songs that are lullabies and a dozen songs that are not lullabies and gather a lot of data from each infant. But an infant’s attention span is short, so the experiment is short too,” said Mila Bertolo, co-first author of the research.

The songs were chosen through a previous Music Lab study, in which adults rated how likely a foreign unfamiliar song was to be a lullaby, a dance song, a healing song, or a love song. Using a cross-cultural sample of adult-rated lullabies helped the researchers avoid incorporating their own selection bias into the process, where they might be more inclined to choose songs that most closely resembled a western lullaby, said Bertolo.

The 16 songs selected for the experiment came from the Natural History of Song Discography, and included lullabies and other songs originally produced to express love, heal the sick, or encourage dancing. Languages like Scottish Gaelic, Hopi, and Western Nahuatl, and regions including Polynesia, Central America, and the Middle East were represented in the songs chosen.

“Melody is one of the things that sticks out for lullabies. In comparison, in a lot of other song types, such as dance songs, you would see rhythm as being more of a driving force,” explained Connie Bainbridge, who co-led the research with Bertolo in the Music Lab, and is now pursuing a Ph.D. in communication at UCLA.

Separately, researchers asked parents to listen to both types of song and choose which they would use to soothe their infant. They almost always chose the lullaby, indicating that they also recognized the universal elements of the lullaby, even subconsciously. “Calming a fussy infant is an urgent matter for parents. Those of us with kids might be particularly sensitive to the acoustic features that appear universally in lullabies, as these may be most likely to calm our infants efficiently,” said Mehr.

The findings are “a testament to how effective music is,” said Bertolo. “This piece of the puzzle helps us make sense of certain kind of downstream effects” like music therapy in clinical settings. “It’s an interesting question to see whether the same thing that drives the relaxation for infants would carry through into adulthood.”

The researchers predict that the results could be replicated with a different group of subjects from another culture. They also plan to continue investigating questions raised during the experiment, such as which of the specific acoustical elements of a lullaby encourage relaxation, how singing interacts with other activities and environments to induce relaxation, and what inferences infants might make during listening.

The research provides evidence that singing can help infants relax—and in doing so might improve daily life for both child and caregiver.

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Haircuts and golf in Melbourne as virus curbs ease

Residents of Australia’s second-biggest city flocked to salons and golf courses Monday as some stay-at-home restrictions were eased after coronavirus infection rates fell.

Melbourne’s five million people had been barred from leaving their homes with a few exceptions—including shopping for essentials, exercising, or going to work—for three months.

They still face a litany of travel restrictions and tough-to-remember rules for even the most mundane activities, but will now be able to get a much-needed haircut and do more outdoor socially distanced activities.

“We’re already fully booked until December,” salon owner Daniel Choi told AFP.

“From yesterday, there are so many messages for me: ‘I want a haircut’. They want to change their style.”

Salon owners still have to contend with restrictions on the number of people allowed on the premises at the same time, meaning those eager to correct self-inflicted dye jobs or improvised trims could face a long wait.

But for the lucky first customers there was a sense of elation.

“It’s a sense of relief actually that finally I could get it done,” said customer Karen Ng.

“It’s nice actually to have some normality.”

Golfers can also tee it up again, although they will have to go around in groups of two and, according to Golf Australia, “masks must still be worn when playing”.

“It’s a great sight… GOLFERS ON COURSE!” Green Acres Golf Club tweeted.

But many restrictions remain in place in the city.

Masks are mandatory, restaurants are limited to takeaways and deliveries, non-essential shops have to remain closed and there is a ban on travel outside the greater Melbourne area or more than 25 kilometres (16 miles) from home.

The city’s second round of stay-at-home restrictions began in July, when the state of Victoria saw around 190 new cases a day, rising to 700 in August.

Victoria recorded just four new cases on Monday.

But not everyone was happy with the limited easing, including Australia’s conservative treasurer Josh Frydenberg, who criticised the regional authorities for not going further.

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‘Sweet 16’ party becomes ‘superspreader’ event in New York

A 16th birthday party in New York state became a super-spreader event with dozens of attendees contracting coronavirus, according to officials.

The September 25 shindig at the plush Miller Place Inn on Long Island left 37 people infected with COVID-19 and forced more than 270 into quarantine.

Over 80 people attended the party, known as a “Sweet 16” in the United States, well above the state’s 50-person limit. The venue has been closed temporarily and fined $12,000, local officials said.

“We’ve never seen a super-spreader event like this before in Suffolk County,” tweeted the area’s county executive on Wednesday.

“People have to act responsibly so that we do not have another economic setback.”

New York state has largely kept coronavirus under control in recent months after 33,000 residents died from the virus, mainly in the spring.

But in recent weeks, infections have multiplied in some areas, especially in neighborhoods with large Orthodox Jewish populations.

Governor Andrew Cuomo closed non-essential businesses and capped places of worship at ten people in the so-called red zones.

New York City Mayor Bill de Blasio defended the measures on Thursday, citing tightened restrictions in Europe where cases are on the rise.

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Coronavirus outbreak linked to spin studio in Canada: officials

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More than 60 cases of the novel coronavirus have been linked to a spin studio in Canada, according to public health officials there. 

Some 61 people have been infected with the virus in connection with an outbreak at the cycling studio Spinco in Hamilton, which is located in the province of Ontario. 

Exposure dates range between Sept. 28 and Oct. 4.
(iStock)

Dr. Elizabeth Richardson, the medical officer of health in Hamilton, said 44 of the cases have been reported among spin studio patrons, while 17 are secondary cases linked to the primary cases. 

"We haven't kept an exact count on how many of those [secondary cases] have had contacts," she said. "In general, we're up to having people having 20 to 25 contacts per case that we investigate … we haven't specifically tracked contacts for this outbreak and don't do that generally,” she said when warning the outbreak could grow larger, according to the Canadian outlet CBC News. 

CLOTH CORONAVIRUS FACE MASKS WORK — BUT ONLY IF YOU DO THIS AFTER WEARING THEM, STUDY FINDS

Exposure dates range between Sept. 28 and Oct. 4. 

It’s not currently clear how the outbreak began, as the studio reportedly has taken “proper pandemic protocol” since reopening, per the outlet. 

"Gyms are a higher risk place because of the fact generally people are taking off their masks, breathing at a higher rate and more deeply, and especially in classes where there's coaching going on, that tends to be a louder tone to speak over music," Richardson said. 

On its website, Spinco lists the precautions it has taken, including enhanced sanitation and social distancing measures. Both staff and members are required to wear masks at all times while in the studio, but class participants are, however, allowed to remove their masks once they are clipped into their bike. 

RISKIEST BEHAVIORS TO AVOID DURING CORONAVIRUS PANDEMIC, ACCORDING TO AN EXPERT

“Instructors must request all riders put their masks back on prior to getting off their bikes at the end of class, and must wear them out of the studio,” the website notes. 

In a statement posted to Instagram earlier this week, the owners of the Spinco studio in Hamilton said that everyone who has tested positive is doing well. 

"We love you and we miss you!" the statement reads in part. "When we started the journey to open a SPINCO franchise in Hamilton, we had a dream of building an inclusive space for everyone to exercise. We got the green light to reopen in July, like everyone we were hesitant, but we took all the measures public health offered, even added a few, and still the pandemic struck us again!" 

"It started September 28 and spread amongst specific classes until October 5th," the post reads. "SPINCO Hamilton has been closed from the moment the outbreak was identified. As of today, everyone who has tested positive, are well. Our team, alongside Public Health has notified everyone. "We have been following all the procedures set in place by public health. We have been in constant contact with our riders and we will continue to do so, if not daily, then every few days, with updates." 

The owners vowed to come back stronger once it's deemed safe to do so. 

"So we are at a point, where either we let this pandemic own us, or we take ownership back. We are determined to switch the script! We can and we know the power of our community," the post read. "So while we wait and remain closed, you have our commitment that we will not re-open until it is safe to do so, we need to show our city and the rest of our province that the SPINCO community is not going anywhere! We are strong, we are tough and we fight together.."  

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In other parts of Ontario, namely Peel, Ottawa, and Toronto, gyms are facing a second closure. But Richardson said officials are continuing to review the outbreak in Hamilton before again shutting down fitness studios there. 

"If we saw something that extended beyond this one particular instance we would definitely move to do something more quickly, but right now … saying make sure you're wearing a mask, make sure you're distancing, turn that music down, don't be yelling …while we look at this and see what more could be done,” she said, according to CBC News. 

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STAT3 identified as important factor in emotional reactivity

Numerous scientific studies indicate that inflammatory processes play a key role in the development of psychiatric disorders. One of the areas of particular interest is the interleukin 6/STAT3 signal transduction pathway, which is associated with depression, schizophrenia, and bipolar disorder. In a study published in Molecular Psychiatry, MedUni Vienna researchers led by Daniela Pollak from the Division of Neurophysiology and Neuropharmacology showed that STAT3 plays an important role in the serotonergic system as a molecular mediator for controlling emotional reactivity, thereby establishing a mechanistic link between the immune system, serotonergic transmission and affective disorders such as depression.

The STAT3 signal transduction pathway is activated in response to a series of immunogenic and non-immunogenic stimuli, i.e. those that can and those that cannot trigger an immune response. “It was found that STAT3 is involved in nervous system functions that are important for controlling behavior in physiological and pathological situations. In an earlier study, we had managed to show that STAT3 also regulates the expression of the serotonin transporter gene (Note: SERT),” explains Pollak.

Changes in serotonergic transmission, that is to say the transmission of information from one neuron to another using serotonin as a messenger substance, correlate closely with pathological changes in depression or other affective disorders. However, the interaction between the STAT3 signal transduction pathway and the neuronal information flow in the brain and its importance in regulating emotional behavior has not yet been explored.

STAT3 deficiency reduces emotional reactivity

The published work therefore specifically investigated the significance of the STAT3 signal transduction pathway in the serotonergic system of the midbrain—an emotional regulation center—by targeted inhibition of STAT3 in a mouse model. Says Pollak: “Where STAT3 was selectively absent from the serotonergic system of the midbrain, the mice displayed reduced, negative emotional reactivity in their behavior and a diminished response to the effects of amphetamine in the brain. These effects could be detected in mice with reduced STAT3 expression both in a genetic and in a viral model, so that it was possible to rule out developmental changes and to show that an acute manipulation of STAT3 in the adult organism impacts on emotional behavior.”

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Research illustrates atypical sensory experiences in early-onset schizophrenia adolescents

Schizophrenia is associated with a wide range of cognitive impairments including sensory information processing. Findings showed that impaired sensory processing, either hypo- or hyper-reactivity to sensory stimuli, is an important marker contributing to the development of psychotic symptoms and cognitive impairments of schizophrenia. Most of the previous studies have primarily focused on the investigation of cognitive processing and neural mechanism of sensory information processing in schizophrenia.

However, it is equally important to understand how specific sensory responsiveness patterns are with the symptomatology of schizophrenia. Moreover, given that schizophrenia and autism are neurodevelopmental disorders having shared cognitive and social dysfunctions, and showing high co-occurrence rates, it is important for us to examine the uniqueness and similarities in sensory responsiveness between patients with schizophrenia and autism. Such an altered sensory responsiveness is much neglected in the extant literature.

Dr. Raymond Chan’s team from the Institute of Psychology has conducted a study to examine sensory responsiveness in 98 typically developing adolescents and 29 adolescents with early onset schizophrenia. They also examined the relationship between schizotypal traits and sensory responsiveness patterns between these two groups.

They administered the Adult/Adolescent Sensory Profile, the Schizotypal Personality Questionnaire and the Autism Spectrum Quotient to all participants.

Their findings showed that higher levels of hypersensitivity and hyposensitivity coexisted in adolescent with early onset schizophrenia and were correlated with positive and negative symptoms of schizophrenia. Positive correlation was found between atypical sensory experiences and higher levels of schizotypal traits.

Interestingly, the strength and pattern of such correlations were found to be comparable in both adolescents with early onset schizophrenia and typically developing adolescents.

Moreover, higher levels of autistic traits would intensify the positive correlation between schizotypal traits and sensory responsiveness abnormalities, suggesting an additive effect of co-occurring schizotypal and autistic traits on atypical sensory experiences.

“These findings contribute to our understanding of the altered sensory responsiveness patterns in early onset schizophrenia. Importantly, these findings may also help us to develop appropriate sensory-related interventions in patients with neurodevelopmental disorders,” said Dr. Chan.

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COVID-19 Taking Huge Toll in Excess U.S. Deaths

TUESDAY, Oct. 13, 2020 — A pair of new studies assert that the U.S. response to the COVID-19 pandemic has been a disaster, causing more deaths than thought and prolonging Americans’ suffering more than any other country.

The United States experienced a 20% increase over expected deaths between March and August 2020, with more than 225,500 people needlessly dying, said the lead researcher on the first study, Dr. Steven Woolf. He’s director of the Virginia Commonwealth University Center on Society and Health, in Richmond.

All of those excess deaths can be laid at the feet of the COVID-19 pandemic and the inadequate U.S. response to it, Woolf said.

According to Dr. Amesh Adalja, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore, “The research on excess mortality from COVID-19 really underscores what many of us have seen on a day-to-day basis. This pandemic was earth-shattering for this country, and the reverberations of the pandemic were felt everywhere and extended even to those who were never infected with the virus.”

As a result, the United States is first among developed nations in the number of citizens per capita who have died due to COVID-19.

Worse, the U.S. pandemic continued on through the summer even as other countries managed to gain control over the new coronavirus, the second study reports.

Between May and September, the United States experienced more than 31 excess deaths per 100,000 people, Dr. Ezekiel Emanuel, of the University of Pennsylvania in Philadelphia, and his colleague found.

By comparison, other countries who have lost many people to COVID-19 — Spain, the United Kingdom, Belgium, France, Sweden — had much lower excess death rates due to the pandemic over the summer, as they adopted tactics to halt transmission of the virus.

For example, Sweden had about 15 excess deaths per 100,000, half as many as the United States, and the United Kingdom had about 14 excess deaths per 100,000.

“We knew it was bad. It’s actually even worse,” said Dr. Harvey Fineberg, president of the Gordon and Betty Moore Foundation in Palo Alto, Calif.

The two new studies and an editorial by Fineberg were published online Oct. 12 in the Journal of the American Medical Association.

The 20% increase in U.S. deaths were all related to the pandemic, but not all were caused by the virus, Woolf said. COVID-19 was a documented cause in only 67% of those cases.

“The calculation of excess deaths shows that for every two Americans that we know are dying from COVID-19, an additional American is dying from causes other than COVID-19,” Woolf said.

The other pandemic-related deaths are due to:

  • People not getting care in emergency situations — for example, “the patient with chest pain who’s scared to call 911 because they don’t want to get the virus, and dies of a heart attack,” Woolf said.
  • Patients dying from chronic conditions like diabetes, cancer and heart problems, because they didn’t have access to the medical care that had helped them control their health problems.
  • People suffering from pandemic-related anxiety, depression or stress who either die by suicide or die from an accidental overdose.

“The opioid epidemic hasn’t gone away,” Woolf said. “People under stress trying to cope with the strains of this pandemic may have taken a drug overdose and died. We suspect some of those excess deaths are from these other causes.”

It’s also likely that at least some of these unexplained excess deaths really are due to undetected COVID-19 infections, Woolf added.

Woolf and his team also found that the U.S. struggle with COVID-19 was compounded by decisions in some states to emerge from lockdown prematurely, without any good plan to control virus transmission.

“States like Florida, Texas, Arizona and others that made the choice to reopen early, like in late April or early May, their curves look very different,” Woolf said. “You see a pattern of initially slowly rising and then surging excess deaths in the summer. That dragged out the length of their epidemic.”

By comparison, U.S. states hit hardest early on — such as New York and New Jersey — had an early spike in mid-April that then fell rapidly “because they did a very good job of controlling community spread,” Woolf said.

Combined with the second study’s global comparison, the studies “together say something very important,” Woolf said.

Other countries have taken effective steps to control the pandemic — comprehensive travel bans, production of personal protective equipment (PPE), access to testing, and public health work like contact tracing.

“You find that the U.S. faltered in each of those steps in a rather dramatic way,” Woolf said.

He pointed to the early travel ban that President Donald Trump often cites as proof that his administration effectively responded to the pandemic.

The ban only applied to Chinese nationals, while other countries “really locked down arrivals into their country in a way that the U.S. did not do,” Woolf said.

“U.S. citizens were still flying in from China, but more importantly the virus was coming from Europe and there was no ban imposed there until March,” Woolf said. “Those kinds of shortcomings in our response have led the U.S. to end up with a mortality rate that is exceeding those of other countries.”

Adalja agreed.

“It is also important to remember that we did not have to have this trajectory with the pandemic,” Adalja said. “There were clear actions that could’ve been taken in January, February and March but were not and are still not.”

The United States failed to swing its industrial might behind an effort to develop a testing strategy, Adalja noted.

The United States “also failed to fortify our public health infrastructure despite the fact we knew that this virus is going to come here and it would be a huge burden on case investigators and contact tracers,” he added. “There was also no effort to augment [personal protective equipment] until it became too late. Imagine if we would’ve started thinking about PPE in January and making strategic buys at that point in order to increase supply.”

All of this has added up to a staggering loss of life that, not coincidentally, has ravaged the U.S. economy, Fineberg said.

“The economic consequences of this pandemic are stunning,” he said. “They estimate it has essentially stripped away almost a full year of the whole nation’s productivity, in their estimate a cost of $16 trillion. That’s made up of both direct health costs and other costs to the economy.”

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Immune cell activation in severe COVID-19 resembles lupus

In severe cases of COVID-19, Emory researchers have been observing an exuberant activation of immune cells, resembling acute flares of systemic lupus erythematosus (SLE), an autoimmune disease.

Their findings point towards tests that could separate some COVID-19 patients who need immune-calming therapies from others who may not. They also may begin to explain why some people infected with SARS-CoV-2 produce abundant antibodies against the virus, yet experience poor outcomes.

The results were published online on Oct. 7 in Nature Immunology.

The Emory team’s results converge with recent findings by other investigators, who found that high inflammation in COVID-19 may disrupt the formation of germinal centers, structures in lymph nodes where antibody-producing cells are trained. The Emory group observed that B cell activation is moving ahead along an “extrafollicular” pathway outside germinal centers—looking similar to they had observed in SLE.

B cells represent a library of blueprints for antibodies, which the immune system can tap to fight infection. In severe COVID-19, the immune system is, in effect, pulling library books off the shelves and throwing them into a disorganized heap.

Before the COVID-19 pandemic, co-senior author Ignacio (Iñaki) Sanz, MD and his lab were focused on studying SLE and how the disease perturbs the development of B cells.

Sanz is head of the division of rheumatology in the Department of Medicine, director of the Lowance Center for Human Immunology, and a Georgia Research Alliance Eminent Scholar. Co-senior author Frances Eun-Hyung Lee, MD is associate professor of medicine and director of Emory’s Asthma/Allergy Immunology program.

“We came in pretty unbiased,” Sanz says. “It wasn’t until the third or fourth ICU patient whose cells we analyzed, that we realized that we were seeing patterns highly reminiscent of acute flares in SLE.”

In people with SLE, B cells are abnormally activated and avoid the checks and balances that usually constrain them. That often leads to production of “autoantibodies” that react against cells in the body, causing symptoms such as fatigue, joint pain, skin rashes and kidney problems. Flares are times when the symptoms are worse.

Whether severe COVID-19 leads to autoantibody production with clinical consequences is currently under investigation by the Emory team. Sanz notes that other investigators have observed autoantibodies in the acute phase of the disease, and it will be important to understand whether long-term autoimmune responses may be related to the fatigue, joint pain and other symptoms experienced by some survivors.

“It’s an important question that we need to address through careful long-term follow-up,” he says. “Not all severe infections do this. Sepsis doesn’t look like this.”

In lupus, extrafollicular B cell responses are characteristic of African-American patients with severe disease, he adds. In the new study, the majority of patients with severe infection were African-American. It will be important to understand how underlying conditions and health-related disparities drive the intensity and quality of B cell responses in both autoimmune diseases and COVID-19, Sanz says.

The study compared 10 critically ill COVID-19 patients (4 of whom died) admitted to intensive care units at Emory hospitals to 7 people with COVID-19 who were treated as outpatients and 37 healthy controls.

People in the critically ill group tended to have higher levels of antibody-secreting cells early on their infection. In addition, the B cells and the antibodies they made displayed characteristics suggesting that the cells were being activated in an extrafollicular pathway. In particular, the cells underwent fewer mutations in their antibody genes than seen in a focused immune response, which is typically honed within germinal centers.

The Nature Immunology paper was the result of a collaboration across Emory. The co-first authors are Matthew Woodruff, Ph.D., an instructor in Sanz’s lab, and Richard Ramonell, MD, a fellow in pulmonary and critical care medicine at Emory University Hospital.

Ramonell notes that the patients studied were treated early during the COVID-19 pandemic. It was before the widespread introduction of the anti-inflammatory corticosteroid dexamethasone, which has been shown to reduce mortality.

The team’s findings could inform the debate about which COVID-19 patients should be given immunomodulatory treatments, such as dexamethasone or anti-IL-6 drugs. Patients with a greater expansion of B cells undergoing extrafollicular activation also had higher levels of inflammatory cytokines, such as IL-6.

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