IT'S SCIENCE  FRICTION MONDAY

Massive U.S. contact tracing effort 'of critical importance'

by Katie Pearce, Johns Hopkins University

Credit: CC0 Public Domain

Before the United States can reopen safely, a new workforce at least 100,000 strong should be in place to trace the contacts of people diagnosed with COVID-19, according to a report from the Johns Hopkins Center for Health Security and other experts.

A long-used public health tool, contact tracing aims to break the chain of transmission of a contagious disease by identifying and alerting those who may have been exposed to it. Traditionally, a trained contact tracer will interview an individual diagnosed with the disease to determine all of their recent contacts, then reach out to those contacts to provide further information—which may include a recommendation to self-quarantine. In the past, this meticulous strategy has been used to help control Ebola, SARS, sexually transmitted infections, and tuberculosis, among other communicable diseases.

With the global outbreak of COVID-19, public health experts believe contact tracing will be a critical step for containing the virus, alongside social distancing and widespread testing. Many countries have already deployed extensive contact tracing, including New Zealand, Iceland, Taiwan, Singapore, and South Korea.

The United States, too, is gradually ramping up efforts—including a new hiring surge funded by the CDC, a Google/Apple tech partnership, and a statewide program in Massachusetts. In New York, Gov. Andrew Cuomo is working with Bloomberg Philanthropies to launch a massive contact tracing program that will include online training from the Johns Hopkins Bloomberg School of Public Health.

"In the absence of a vaccine, we think this is really the big public health tool we have to control transmission of COVID-19," says Crystal Watson, a lead author of the new report and assistant professor in the Bloomberg School. "We need to push hard for this."

The report acknowledges that a contact tracing effort of this magnitude—"and of this critical and historical importance for the functioning and reopening of society"—is without precedent. In an interview with the Hub, Watson offered more insight on the significance of this approach and the challenges ahead.

Is contact tracing on the scale the report suggests achievable in this country?

It's going to take a lot of work and some imagination and probably changing the rules in some ways to do things differently—but I do think it's achievable. We're seeing that other countries have implemented contact tracing and are able to contain the virus at a relatively low level in their communities.

We're also seeing parts of the U.S. start to put this in place, so that's encouraging, but it's not enough. We need to hire what we believe is up to 100,000 people or more to complete this work. So what we need first is funding and commitment from the federal government and Congress, to really scale this up in a way that's required. Our report suggests the need to dedicate approximately $3.6 billion for state and territorial health departments to make contact tracing wide-scale.

What are the likely outcomes if we try to reopen the country without robust contact tracing in place?

We don't know exactly how many people are still susceptible to COVID-19, but we're relatively confident that it's a very large percentage of our population. So if we reopen and we don't have the capacity to find each case, isolate them, then trace their contacts and put them in quarantine, this virus will start to circulate widely again in our communities, and we will see again a big surge of cases, a surge of hospitalizations, and a surge of deaths. If we don't reinforce these measures, things may get a lot worse.

As the report notes, privacy protections in the U.S. may prevent aspects of contact tracing we're seeing in other countries. What are the implications of that?

The U.S. won't be able to replicate a contact tracing effort like the one in South Korea, for example, which can use medical records, phone GPS records, credit card transactions, and closed-circuit TV.

We need to have conversations here about how to sufficiently protect privacy in this context. But there has to be a balance between personal privacy and getting health departments the information they need to act quickly. The Google and Apple partnership [to offer Bluetooth-enabled apps to track potential exposure to COVID-19] is promising, but it's unclear how public health officials will be able to use that information. I don't think we've struck that right balance yet with the technologies that are out there.

As unemployment skyrockets, to what extent can contact tracing create a new source of jobs?

This is a huge workforce that we need to engage. It may include many types of people: public health experts, retired health care workers, but also people outside the field. Contact tracing is an intensive activity, but it doesn't take a lot of time to train staff. We need people who are meticulous, who can make people comfortable and treat the task with sensitivity. Fluency in different languages is also a plus because we need to reach all communities.

So I think this is a great opportunity to put people to work who have either been laid off because of the pandemic, or who otherwise just want to be directly involved in the response.

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NZ needs COVID-19 contact tracing to make nationwide lockdown worthwhile

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More information: A National Plan to Enable Comprehensive COVID-19 Case Finding and Contact Tracing in the US.
https://www.centerforhealthsecurity.org/our-work/pubs_archive/pubs-pdfs/2020/200410-national-plan-to-contact-tracing.pdf

Provided by Johns Hopkins University

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Saliva samples preferable to deep nasal swabs for testing COVID-19

by Michael Greenwood, Yale University

Credit: CC0 Public Domain

As testing for the novel coronavirus continues to scale up, a new study finds that saliva samples are a "preferable" indicator for infection than the deep nasal swabs now widely used.

The study led by the Yale School of Public Health—and conducted at Yale New Haven Hospital with 44 inpatients and 98 health care workers—found that saliva samples taken from just inside the mouth provided greater detection sensitivity and consistency throughout the course of an infection than the broadly recommended nasopharyngeal (NP) approach. The study also concluded that there was less variability in results with the self-sample collection of saliva.

"Taken together, our findings demonstrate that saliva is a viable and more sensitive alternative to nasopharyngeal swabs and could enable at-home self-administered sample collection for accurate large-scale SARS-CoV-2 testing," said first author Anne Wyllie, an associate research scientist at the Yale School of Public Health and a member of its Public Health Modeling Unit. She was joined by 49 other researchers at Yale on the study.

The researchers also reported that the saliva approach detected SARS-CoV-2 in two asymptomatic health care workers who had previously tested negative for the virus in a NP swab test. Saliva testing may be especially useful due to its accuracy in identifying mild SARS-CoV-2 infections that are not detected with other methods, the researchers said.

More sensitive and consistent detection is expected to be critical in helping to assess when individuals are able to safely return to work and when local economies can reopen during the current pandemic.

The study has not been subject to peer review. The research results are currently available on the pre-print server medRxiv. The researchers called for the "immediate validation" of the results. Nasopharyngeal testing is considered the gold standard for detecting many upper respiratory tract pathogens.

The study noted that saliva is an appealing alternative to NP swabs because:

• Collecting saliva is minimally invasive to patients.
• Saliva samples can be reliably self-administered.
• Saliva has exhibited comparable sensitivity to nasopharyngeal swabs in detection of other respiratory pathogens.

The NP testing approach involves inserting a swab deep into the nostril and into the region of the pharynx. The swab is rotated to collect secretions and is then removed. The sample is then sent to a certified lab for analysis.

On April 13, the U.S. Food and Drug Administration gave emergency use authorization for a saliva-based test for COVID-19 developed by researchers at RUCDR Infinite Biologics, a biorepository backed by Rutgers University. The approved test must be conducted in a healthcare setting under supervision of a qualified professional.

"With further validation, widespread use of saliva sampling could be transformative for public health efforts," said Wyllie.

Saliva testing requires less resources, personal protective equipment, and personnel than nasopharyngeal swabbing, the researcher said.

"Once tests and laboratories are validated for using saliva, this could be rapidly implemented and immediately resolve many of the resource and safety issues with SARS-CoV-2 testing," said Nathan Grubaugh, an assistant professor at the Yale School of Public Health and one of the senior authors of the study.

COVID-19 saliva tests: What is the benefit?More information: Anne Louise Wyllie et al. Saliva is more sensitive for SARS-CoV-2 detection in COVID-19 patients than nasopharyngeal swabs, (2020). DOI: 10.1101/2020.04.16.20067835

Provided by Yale

Why aren't there enough ventilators and hospital beds? Anti-trust laws have a lot to do with it.

by Khalida Sarwari, Northeastern University

Credit: CC0 Public Domain

Around the world, ventilators—a life-saving medical device that keeps air flowing into the lungs of a patient who is unable to breathe—are a scarce resource in hospitals and clinics where they're used to treat those infected with the COVID-19 virus.

The machines are expensive, complex, and they take a long time to make. They're also produced by only a handful of manufacturers, among them Medtronic, a medical equipment company that specializes in such devices. In response to the pandemic, the company has agreed to nearly double its production capacity, and recently offered to share its ventilator technology with other companies in order to accelerate production.

But if the antitrust laws regulating mergers and acquisitions by the Federal Trade Commission had been more stringent a few years ago, says economist John Kwoka, there wouldn't be such a limited number of suppliers dominating the ventilator market, which as a result has left us vulnerable to a shortage during a public health emergency.

"Everyone's concerned about how we got into this circumstance," says Kwoka, Neal F. Finnegan distinguished professor of economics at Northeastern. "And the answer is some of it was the result of planning too close to the margin, but some of it was the willful acts of companies seeking to prevent competition."

The Federal Trade Commission has shown a tendency over the past 20 years not to challenge mergers until the field of competition is smaller. The agency has also looked for benefits or reasons to approve mergers, says Kwoka, whereas in the old days, it took a more cautious approach, approving mergers only if they were clearly harmless or even beneficial.

One consequence of that has been a rapid consolidation in the medical equipment markets where a single company has ended up acquiring other relatively smaller companies that represented either competitive threats or overlapping possibilities.

"As a result of that process of consolidation, we have a much smaller number of very large companies with huge portfolios of products instead of a larger number of competitors in any single market," Kwoka says.

Similarly, the hospital industry has also undergone dramatic consolidation in the last 15 to 20 years—to the tune of close to 800 acquisitions, Kwoka says, many by hedge funds seeking to quickly maximize their bottom line.

This has left many communities, especially in rural areas, without a single hospital, and contributed to the steady decline and current shortage of beds across the country amid the pandemic.

"The Federal Trade Commission again has really not been active in challenging enough of these," says Kwoka. "They try to challenge some, to their credit, but with a tidal wave of mergers, it's been difficult for them to do anything other than take a look at the leading and largest examples."

The Medtronic case goes back to 2013 when, in an effort to supplement the national inventory, the U.S. Department of Health and Human Services contracted with Newport, a small startup supplier of ventilators. The department put out a series of specifications requiring a certain number of units and at one-third the price than the ones that were being produced by the major ventilator manufacturers in the country at the time, which included the Dutch firm Philips, and eventually a company called COVIDien (which was later acquired by Medtronic).

Newport had already produced some test models that met the specifications, says Kwoka. Nevertheless, the company was bought by COVIDien, which demanded a bigger contract from the government, and when the government only partially acquiesced, COVIDien withdrew from the contract and none of these new ventilators was produced.

"A number of observers at the time, and some government officials, thought—not surprisingly—that part of COVIDien's plan was simply to eliminate a lower cost potential competitor to its traditional ventilator operation," says Kwoka.

Consequently, he says, the effort to produce small, cheaper ventilators in large numbers to supplement the country's stockpile collapsed. The health and human services department eventually entered into a new contract with Philips, but years were wasted and that agreement still has yet to produce any ventilators.

"The long and short of it is that COVIDien wanted to keep a potential competitor—a cheaper substitute for its own equipment—off the market, and succeeded in doing so," Kwoka says.

The Federal Trade Commission, upon completing a cursory review of the COVIDien acquisition, deemed that it was not a competition issue, and therefore did not challenge it.

While it's "nearly impossible" to undo the existing acquisitions, Kwoka suggests that going forward, the Federal Trade Commission can be more vigilant about preventing similar mergers in the medical equipment area. And to address the shortage, he says that the major ventilator manufacturers can, as Medtronic has now agreed to do, disclose its designs to enable other companies to manufacture the devices.

Kwoka's forthcoming book, Controlling Mergers and Market Power: A Program for Reviving Antitrust in America, addresses the question of how to reform and revitalize antitrust policy, and merger control in particular, in the U.S, and provides a comprehensive roadmap for rebuilding the necessary policies, institutions, and practices of a vigorous merger control poli

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Provided by Northeastern University

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The coronavirus was in the US in January: We need to understand how we missed it

by Laura Castañón, Northeastern University

Credit: CC0 Public Domain

Back in January, the "novel coronavirus" that had sprung up in the Chinese city of Wuhan was at most a distant worry for many people in the United States.

But SARS-CoV-2, the coronavirus that causes COVID-19, was already circulating in major U.S. cities, according to Alessandro Vespignani, Sternberg Family distinguished university professor, who directs Northeastern's Network Science Institute. And if we want to keep our communities safe going forward, we need to understand how we missed a virus that was right under our noses.

"We don't want to fall into this trap in the future," Vespignani says.

The discovery that the virus was already circulating in the U.S in January comes from a model that Vespignani and his colleagues have been using to study and predict the global spread of the virus. The model relies on human mobility and patterns of interaction, as well as the infection dynamics of the virus.

"The model allows us to go into what we call the invisible stage of the epidemic in the United States," Vespignani says. "We can simulate the arrival of infected people that were starting local transmission chains."

Research that the group released last month shows that the cordoning off of cities within China, as well as travel restrictions implemented by countries around the globe, came too late. The coronavirus was already out.

But how did we miss it? Why didn't we notice people getting sick?

"There was no large scale testing capacity in the US and Europe, and the guidelines were to test only people with a travel history," Vespignani says. "But when you get an infection from somebody who is already in the United States, you don't have a travel history."

It was January—the height of flu season, winter colds, and other respiratory illnesses. Even the few people with severe cases would not have drawn much attention without a history of recent travel to China.

"So what happened is that for a month and a half, the epidemic had gone unnoticed," Vespignani says. "Until you have a critical mass of cases. Then, at that point, you start to see the tip of the iceberg."

Cities that are hubs for international travel from China—New York, Seattle, San Francisco, Los Angeles—saw the earliest cases in the U.S. But similar chains of infection were beginning all over the world. By the time the U.S. was turning away or quarantining travelers from China, the coronavirus was already spreading through U.S. cities, and new cases were coming from Europe and other areas.

Given the amount of change our lives have undergone in the past few months, looking back to January may feel like ancient history. But understanding how and when these outbreaks started can help researchers make predictions down the line.

"If I have an epidemic that starts in early January, I can project a certain trajectory; if I have an epidemic that starts in early March, everything is shifted by two months," Vespignani says. "That's an infinite time for a disease like this one. So you really want to be as sharp as possible, down to the level of a single week, to have the right timeline now to inform what we will see in the next weeks or months."

And what the researchers are learning will also help us make smart decisions when the number of infections has dropped off and we begin to lift physical-distancing measures.

It wasn't enough to only test for the virus based on travel history to national or international hotspots, Vespignani says. If we don't have more extensive testing, and the ability to trace the contacts of each infected person, a second wave of infection could be building without our knowledge.

"We don't want to find ourselves in the same situation," Vespignani says. "We need to have all that so that we can make visible what, in principle, could be invisible."

Provided by Northeastern University 

Lithium may treat behavior linked to autism gene
by Peter Hess, Brandeis University

Altered responses: Neurons in mice missing a gene called SHANK3 do not respond well to changes in sensory input. Credit: Brandeis University

The mood-stabilizing drug lithium eases repetitive behaviors seen in mice missing SHANK3, an autism gene, according to a new study1.

The findings suggest lithium merits further study as a treatment for some people with autism, even though the drug has troublesome side effects, including tremors and impaired memory.

"Lithium is, of course, a rather difficult, non-ideal treatment," says lead investigator Gina Turrigiano, professor of vision science at Brandeis University in Waltham, Massachusetts. "It's really hard to get people on a lithium regimen that they can tolerate well." But understanding why lithium works may set the stage for better treatments, she says.

About 1 percent of people with autism have mutations in SHANK3. Deletion or mutation of the gene can also lead to Phelan-McDermid syndrome, which is characterized by intellectual disability, delayed speech and, often, autism.

Case studies of people with Phelan-McDermid syndrome also suggest that lithium eases behavior problems associated with the condition2.

Previous work has shown that SHANK3 helps stabilize neuronal circuits by adjusting excitatory and inhibitory signaling like a thermostat. This process, called homeostatic plasticity, allows neurons to respond to changes in sensory input.

The new study suggests the gene controls this thermostat by regulating how frequently neurons fire and how they adjust the electrical currents flowing through them. SHANK3 loss or mutation prevents neurons from adapting to changes in sensory input.

"What we've shown is there's this cellular mechanism, and loss of that mechanism is a direct result of a loss of SHANK3," Turrigiano says.

Firepower

The team first recorded electrical activity in rat neurons in which SHANK3 expression was partially disrupted. They artificially blocked the neurons' ability to fire. The mutant neurons' rate of firing did not return to its original range afterward as it did in control cells, the team found.

The neurons also responded with less electrical activity than controls did when the researchers blocked and then restarted electrical currents. This suggests the mutant neurons had lost their ability to adjust the current flowing through them.


Excitatory neurons in the cortex called pyramidal cells are most strongly affected. Lithium restored the cells' ability to adjust both their firing rates and how much current they carry.

To examine how neurons in mice lacking SHANK3 respond to changes in sensory input, the team implanted electrode arrays into the visual cortex of the mutant mice and controls and glued one eye shut in each mouse.

Over the following three or four days, the neurons in both groups of mice decreased how frequently they fired. But the decrease in the mutant mice was more gradual, suggesting that they take longer to adjust.

Neurons in the control mice returned to their typical firing rate two days after the rate had slowed to its lowest level, presumably because the mice's brains had adapted to the loss of vision in one eye. But in the mutant mice, the neurons never returned to their original firing rates, indicating that without the gene, their brains could not adapt.

The mutant mice also groom themselves excessively, a behavior that is thought to align with obsessive or repetitive behaviors in people. To the researchers' surprise, lithium stopped this behavior entirely. The work appeared in March in Neuron.

Treatment potential

The findings support the idea that lithium may help treat people with SHANK3 mutations, and perhaps those with other forms of autism as well, says Jean Martin Beaulieu, associate professor of psychiatry and neurosciences at the University of Toronto in Canada, who was not involved in the study.

However, he says, the study does not prove that the problems with homeostatic plasticity cause the repetitive behavior. Overgrooming is a complex behavior involving multiple brain areas, he says, whereas the study examined only the visual cortex.

It is also unclear whether lithium acts directly on SHANK3 or on some other target in the circuit, says Thomas Bourgeron, professor of genetics at the Institut Pasteur in Paris, France, who was not involved in the study.

Turrigiano says the loss of SHANK3 may be just the first step in a process that leads to neurons' inability to adapt to sensory input. Identifying which part of that process lithium corrects may point to new targets for treatment, she says.

Turrigiano's team is studying how SHANK3 helps balance excitatory and inhibitory activity of neurons, to better understand its role in maintaining homeostatic plasticity.

New study may explain why people with autism are often highly sensitive to light and noise

More information: Vedakumar Tatavarty et al. Autism-Associated Shank3 Is Essential for Homeostatic Compensation in Rodent V1, Neuron (2020). DOI: 10.1016/j.neuron.2020.02.033

Sylvie Serret et al. Lithium as a rescue therapy for regression and catatonia features in two SHANK3 patients with autism spectrum disorder: case reports, BMC Psychiatry (2015). DOI: 10.1186/s12888-015-0490-1

Journal information: Neuron


Provided by Brandeis University

Commonly used chemicals associated with miscarriage, study finds

by Michael Greenwood, Yale University

Researchers at the Yale School of Public Health have found that maternal exposure to synthetic chemicals widely used in food packaging and commonly found in drinking water supplies is associated with a woman's risk for miscarriage in the second trimester.

All women in the Danish cohort studied had detectable and multiple types of per- and polyfluoroalkyl substances (PFAS) in their pregnancy serum. The study estimated a nearly 80% to 120% increased risk for miscarriage in women with the highest level of two common PFAS compounds, compared with those in the cohort with the lowest PFAS levels. Some positive associations, though in smaller magnitudes and less consistent, were also reported for exposure to other types of PFAS compounds evaluated.

TRUMP AND EPA PUSH BACK CLAIMING PFAS ARE NOT DANGEROUS!!!!

The association was stronger among women who had already borne children, and the researchers said that the results need to be replicated. The study is published in the journal Environmental Health Perspectives.

PFAS, introduced in the 1940s, are widely used in the manufacture of everyday products around the globe—from cookware, to clothing, carpets, and firefighting foam. PFAS are also used in industries such as aerospace, automotive, construction, electronics, and the military. Production of the two most common types of PFAS has been phased out by U.S. manufacturers over concerns about the impacts on the environment and human health, but other compounds in the PFAS family are being produced as replacements. PFAS usage in commercial products is not currently regulated in the United States.

"Policy regulation of PFAS exposure should consider adverse effects on maternal and child health, which have repeatedly suggested that these are vulnerable populations that need to be protected from exposure to these widespread chemicals," said Zeyan Liew, the study's lead author and an assistant professor in the department of Environmental Health Sciences at the Yale School of Public Health.

"More studies should follow up to investigate whether PFAS, widespread pollutants that are affecting nearly all pregnancies in the general population, are a modifiable risk factor for miscarriage," he said. Miscarriage is rather common and affects about 10% to 20% of all clinically recognized pregnancies.

Previous toxicological studies have suggested that high doses of PFAS exposure can cause pregnancy loss and infant deaths in rodents. However, whether PFAS exposure affects the risk of miscarriage in the general population was unclear. This is the largest epidemiological study based on pregnant women enrolled in the Danish National Birth Cohort and compared 220 women who carried their pregnancies through birth with 220 who experienced a miscarriage in the second trimester.

Maternal serum samples were collected in early gestations (around week eight) in the cohort, where the researchers measured the serum-level of several common PFAS compounds in these women. The PFAS exposure level in this pregnancy cohort in Denmark is similar to the exposure level reported in the studies of U.S. general population.

"Mechanistic studies are needed to elucidate the possible biological mechanisms that explain these associations," Liew said. "Moreover, larger epidemiological studies are needed to replicate our findings, evaluate the possible threshold or dose-dependent effects of PFAS exposure on pregnancy loss, and address confounding by pregnancy history."

Fecal excretion of PFAS by pets

More information: Zeyan Liew et al. Maternal Plasma Perfluoroalkyl Substances and Miscarriage: A Nested Case–Control Study in the Danish National Birth Cohort, Environmental Health Perspectives (2020). DOI: 10.1289/EHP6202

Journal information: Environmental Health Perspectives 

 by Yale University 

Shortage of hydroxychloroquine hits mothers with lupus

by Andrew J. Wight, SciDev.Net

Experts warn of babies being at risk over global shortage of hydroxychloroquine caused by COVID-19 panic. Credit: Marco Verch (CC BY 2.0)

Pregnant lupus sufferers and their babies are at risk as global supplies of an anti-malarial medicine used to treat the disease run dry due to COVID-19 panic.

Health experts in the global South warn that the shortage puts babies at more risk of being born with symptoms of the painful auto-immune disease lupus.

Hydroxychloroquine (HCQ), a less toxic derivative of chloroquine, has been approved for treating auto-immune diseases and malaria since the 1950s. US President Donald Trump promoted the drug as a potential COVID-19 treatment and US government departments made bulk purchases, even as studies began to emerge that the drug offered no protection from COVID-19.

The Indian Council of Medical Research has recommended HCQ as a preventative treatment for healthcare workers. Medical doctors voiced their concern in The Lancet that "in this environment of global panic, an endorsement by the highest scientific body of India (and also by the President of the U.S.) will create an overly optimistic perception of the effectiveness of hydroxychloroquine among the public," leading to self-medication and, ultimately, shortages.

Utibe Effiong, a physician at MidMichigan Health and assistant professor of medicine at Central Michigan University, tells SciDev.Net the resulting hoarding and diversion of HCQ is putting lupus patients—particularly pregnant women—at risk, citing the tens of thousands of lupus patients in his home country of Nigeria.

"Supply has reduced drastically due to air and land border closures in Nigeria as a result of COVID-19," Effiong says. "The manufacturing countries have temporarily shut exports to conserve the medications for their population and HCQ has jumped from 2000 Nigerian Naira (US$5.50) per pack of 30 tablets to N12,500 (US$34.70) per pack."

Effiong says the supply of HCQ in Nigeria and much of the developing world comes from Asia and those manufacturers are likely to prefer to sell to the highest bidder.

Ninety percent of the more than five million lupus patients worldwide are women, usually aged between 15 and 44, according to figures from the Lupus Foundation of America. These women tend to have higher maternal mortality, fewer live births, and more complications during pregnancy, a review of studies in the developing world found.

Sebastián Herrera, a rheumatologist based at Medellín General Hospital and CES University in Colombia, says that despite Colombia having many manufacturing facilities for HCQ, the unexpected increased demand means that the medicine is no longer available via pharmacy websites and it has become difficult to obtain, especially outside Colombia's major cities.

The Latin American country has had nearly half a million cases of lupus reported in the past five years, mainly impacting women.

According to Herrera, the biggest impact of a HCQ shortage is going to be on pregnant lupus patients and their newborns, as HCQ is one of the few medicines that can reduce the risk of giving birth to children with lupus symptoms.

"In some women with certain types of antibodies that increase the risk of complications for the baby (neonatal lupus), hydroxychloroquine decreases the risk of this complication—if there is no availability, there would be no other option to reduce this risk," Herrera says, adding that switching to other drugs may increase the risk of infections by altering the function of the patient's immune system.

In addition, Herrera says the scarcity of HCQ could lead to disease relapses in other patients, which leads to increased fatigue, absenteeism from work, deterioration in mental health, as well as increased pain.

Akpabio Akpabio, a rheumatologist at the University of Uyo Teaching Hospital in Nigeria, says in his region of southern Nigeria, shortages are starting to bite.

"From my own personal experience, up to 60 percent of lupus patients are currently experiencing shortages in HCQ—some still have it but many of them are running out," he says.

One of the first major papers to discuss the impact of the COVID-19 crisis on lupus patients observed a few missed doses of HCQ may not be critical, but a prolonged shortage could lead to significant consequences.

This has led to some hard choices, Akpabio says, because there is no consensus in the literature on how far and for how long patients can reduce their dosages and still receive the protective effects of the medicine.

Journal information: The Lancet 

Provided by SciDev.Net

FDA warns of heart risks with Trump-promoted malaria drug
by Matthew Perrone and Marilynn Marchione

This Tuesday, April 7, 2020 file photo shows a bottle of hydroxychloroquine tablets in Texas City, Texas. On Friday, April 24, 2020, the U.S. Food and Drug Administration warned doctors against prescribing the malaria drug to treat COVID-19 outside of hospitals or research settings. (AP Photo/David J. Phillip)The U.S. Food and Drug Administration on Friday warned doctors against prescribing a malaria drug touted by President Donald Trump for treating the new coronavirus except in hospitals and research studies.

In an alert, regulators flagged reports of sometimes fatal heart side effects among coronavirus patients taking hydroxychloroquine or the related drug chloroquine. The decades-old drugs, also prescribed for lupus and rheumatoid arthritis, can cause a number of side effects, including heart rhythm problems, severely low blood pressure and muscle or nerve damage.

The warning comes as doctors at a New York hospital published a report that heart rhythm abnormalities developed in most of 84 coronavirus patients treated with hydroxychloroquine and the antibiotic azithromycin, a combo Trump has promoted.

Both drugs are known to sometimes alter the heartbeat in dangerous ways, and their safety or ability to help people with COVID-19 is unknown. A National Institutes of Health experts panel earlier this week recommended against taking that drug combo except in a formal study because of the side effects potential.

Last month, the FDA authorized limited use of the malaria drugs for hospitalized patients with COVID-19 who aren't enrolled in ongoing research. The FDA said the drugs' risks are manageable when patients are carefully screened and monitored by doctors. A number of studies are testing hydroxychloroquine as a treatment or for prevention of COVID-19.

Regulators said they are now investigating dangerous side effects and deaths reported with the malaria drugs to poison control centers and other health authorities.



"It is important that health care providers are aware of the risks of serious and potentially life-threatening heart rhythm problems that can occur with these drugs," the FDA said in a statement. The agency did not specify the number of reports it has received of side effects or deaths.

Calls to U.S. poison control centers about the malaria drugs increased last month to 79, compared to 52 for March 2019, according to Dr. Christopher Hoyte of the Rocky Mountain Poison Center in Denver, Colorado.

The problems reported include abnormal heart rhythms, seizures, nausea and vomiting, Hoyte said.

Trump has repeatedly touted hydroxychloroquine during his regular coronavirus briefings, suggesting its skeptics would be proved wrong. He has offered patient testimonials that the drug is a lifesaver.

But a number of early coronavirus studies have suggested problems or no benefit.

In Friday's report in the journal Nature Medicine, doctors at New York University and NYU Langone Health found a significant prolonging of what's called the heart's QT interval two to five days after coronavirus patients were given usual doses of hydroxychloroquine and azithromycin. The drugs can alter the QT interval, or the time it takes the heart to charge between beats. When that time is too long, it can trigger a rhythm problem that can lead to sudden death.

Nine of the 84 patients had severe prolongation of this interval. Four patients died from organ failure but there was no evidence heart problems contributed. Severe disease or other health problems may play a role in whether the heartbeat abnormality develops, the researchers speculated.

The results show how important it is that these drugs only be used in a study where patients are closely tracked, said one independent expert, Dr. Rais Vohra, an emergency medicine specialist at the Fresno branch of the University of California, San Francisco.

"That combination really sets you up for having a problem with the heart," he said. "My colleagues and I are concerned. People are self-medicating and coming down with very predictable side effects on the heart."

Another recent analysis involving 368 patients in U.S. veterans hospitals found no benefit from hydroxychloroquine—and more deaths. The report was not a rigorous test of the drug and results have not yet been reviewed by other scientists but are the largest so far of its use in COVID-19 patients.

Last month, the federal government accepted more than 30 million doses of hydroxychloroquine and chloroquine donated to the national stockpile by drugmakers Sandoz and Bayer. Since then, more than 20 million doses have been distributed to state and local health officials, according to the Department of Health and Human Services.

Accepting the donation required sign off by both the FDA and the Biomedical Advanced Research and Development Authority, or BARDA, a unit of HHS that obtains treatments to combat bioterrorism and infectious diseases.

Earlier this week, former BARDA director, Rick Bright, said he was demoted from his job leading the agency because he resisted political pressure to allow widespread use of hydroxychloroquine. He has called for a federal investigation and reinstatement to his original job.

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More information: Ehud Chorin et al. The QT interval in patients with COVID-19 treated with hydroxychloroquine and azithromycin, Nature Medicine (2020). DOI: 10.1038/s41591-020-0888-

Journal information: Nature Medicine

EULAR: Hydroxychloroquine use in lupus patients 'does not seem to prevent COVID-19'

by European League Against Rheumatism (EULAR)

Credit: CC0 Public Domain

The current outbreak of COVID-19 represents a source of concern for the management of systemic

lupus erythematous, SLE, patients. These patients have an increased risk of severe infections due to their underlying disease, the use of immunosuppressive drugs, as well as the potential presence of organ damage associated with their disease.

Hydroxychloroquine, HCQ, a drug that is currently part of the long-term care treatment for SLE, has been reported to possess anti-viral activity in vitro and recent publications have suggested a beneficial effect on COVID-19.

The Annals of the Rheumatic Diseases has published a letter this week regarding the impact of COVID-19 on SLE patients taking hydoxychloroquine: "Clinical course of Coronavirus Disease 2019 (COVID-19) in a series of 17 systemic lupus erythematous patients under long-term treatment with hydroxychloroquine."

EULAR Past-President Professor Johannes W. Bijlsma says, "This gives a first clinical picture of the course of COVID-19 in SLE patients treated with HCQ. It paves the way for a larger observational study to identify the risk factors associated with the occurrence of a severe form of COVID-19 in patients with SLE. Our preliminary conclusion, based on the observation that most of the SLE patients in this study received long-term treatment with HCQ, having blood concentrations of the drug within therapeutic range, is that HCQ does not seem to prevent COVID-19, at least its severe forms, in patients with SLE."

Medicine shortages are a significant challenge for people with rheumatic and musculoskeletal diseases in the ongoing situation around COVID-19. Data collected by EULAR shows that a majority of countries in Europe have encountered and are still encountering serious shortages of hydroxychloroquine (HCQ), and that shortages in essential medicines were also encountered before the COVID-19 pandemic. EULAR advises that the unrestricted access to HCQ for a possible COVID-19 prophylaxis in the absence of evidence from clinical trial data should be avoided and the drug rather continue to be available for those who are in need of it, for example for use in the case of a disease in which it has already been long approved.

Systemic Lupus Erythematous is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary from mild to severe and can include painful and swollen joints among other factors. There are often periods of illness, called flares, as well as remission in which there are fewer symptoms.

EULAR has launched the COVID-19 rheumatic and musculoskeletal diseases reporting database, a European paediatric and adult database to monitor and report outcomes of COVID-19 occurring in patients with rheumatic and musculoskeletal diseases with the support of the Global Rheumatology Alliance: https://www.eular.org/eular_covid19_database.cfm

EULAR has released guidance for patients in the context of the COVID-19 outbreak.The guidance addresses typical questions that patients with RMDs have and recommends protective measures both for patients and the health care workforce.More information and a video can be found here: 

EULAR launches COVID-19 RMD reporting database as part of Global Rheumatology Alliance

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More information: Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine. Annals of the Rheumatic Diseases, 24 April 2020. DOI: 10.1136/annrheumdis-2020-217566

Journal information: Annals of the Rheumatic Diseases 

Provided by European League Against Rheumatism (EULAR)