An Orthodox Jewish school in New York City canceled classes on
Tuesday to allow for precautionary measures after a suspected case of
coronavirus turned up within its community.
The SAR Academy and SAR High School in the Riverdale section of the
Bronx borough said it was in touch with the city’s Department of Health
and following its guidelines.
“At this time it important to remain calm,” a statement from school officials said.
The co-educational school, which describes itself as “modern
Orthodox,” urged people to follow steps to prevent and minimize the
spread of the infection, which had led to the reported deaths of six
people in the United States as of Monday evening. About 100 people have
tested positive for the virus, including one person in New York City.
https://www.reuters.com/article/us-health-coronavirus-usa-school/new-york-city-school-cancels-classes-after-suspected-coronavirus-case-idUSKBN20Q1U6?il=0
Tuesday, March 3, 2020
U.S. sues Mallinckrodt, accuses drugmaker of defrauding Medicaid
The United States sued a unit of the drugmaker Mallinckrodt Plc on
Tuesday, accusing it of defrauding Medicaid out of hundreds of millions
of dollars as a result of “extraordinary” price increases for its drug
Acthar Gel.
The government joined a civil lawsuit by a whistleblower who said Mallinckrodt ARD LLC’s conduct concerning Acthar, which is used to treat a rare infant seizure disorder as well as multiple sclerosis, violated the federal False Claims Act.
Mallinckrodt and an outside spokesman did not immediately respond to requests for comment.
The government said that under the Medicaid Drug Rebate Program, drugmakers must pay quarterly rebates to state Medicaid programs in exchange for Medicaid’s coverage of their drugs.
Mallinckrodt was accused of violating a rule designed to shield
Medicaid when drug prices rise faster than inflation, where rebates are
calculated based on a drug’s price in 1990 or the date the drug was
first marketed, whichever is later.
The government said that while Acthar was first marketed in the 1950s, Mallinckrodt and its predecessor Questcor calculated rebates as though marketing began in 2013, by which time the price per vial had risen by more than $20,000, despite being warned not to do this.
By avoiding the payment of inflationary rebates on pre-2013 price increases, Mallinckrodt has cost American taxpayers hundreds of millions of dollars, the government said.
https://www.reuters.com/article/us-usa-mallinckrodt-lawsuit/u-s-sues-mallinckrodt-accuses-drugmaker-of-defrauding-medicaid-idUSKBN20Q2FV?il=0
The government joined a civil lawsuit by a whistleblower who said Mallinckrodt ARD LLC’s conduct concerning Acthar, which is used to treat a rare infant seizure disorder as well as multiple sclerosis, violated the federal False Claims Act.
Mallinckrodt and an outside spokesman did not immediately respond to requests for comment.
The government said that under the Medicaid Drug Rebate Program, drugmakers must pay quarterly rebates to state Medicaid programs in exchange for Medicaid’s coverage of their drugs.
The government said that while Acthar was first marketed in the 1950s, Mallinckrodt and its predecessor Questcor calculated rebates as though marketing began in 2013, by which time the price per vial had risen by more than $20,000, despite being warned not to do this.
By avoiding the payment of inflationary rebates on pre-2013 price increases, Mallinckrodt has cost American taxpayers hundreds of millions of dollars, the government said.
https://www.reuters.com/article/us-usa-mallinckrodt-lawsuit/u-s-sues-mallinckrodt-accuses-drugmaker-of-defrauding-medicaid-idUSKBN20Q2FV?il=0
Race in full-stride for tests to identify coronavirus illness
Abbott (ABT -1.5%), French biotech bioMérieux (OTCPK:BMXMF +3%) and Co-Diagnostics (CODX -7.7%), along with public health labs and hospitals, are working feverishly (no pun intended) to develop tests to spot coronavirus-related illness.
At present the only available FDA-approved tests
are from the CDC and state of New York and this has not been
problem-free. Some of the CDC’s molecular tests that it shipped to other
labs didn’t work properly and had to be replaced. Also, all presumptive
positives require confirmation at the CDC lab in Atlanta.
The FDA has communicated with more than 70
developers and public health labs about their respective tests. The New
York State Department of Health is testing samples and is providing
instructions to hospitals to replicate the test on-site with a goal of
processing about 1,000 tests each day.
A test developed at Hackensack Meridian Health,
operator of 17 hospitals in northern New Jersey, can generate
presumptive results in ~two hours, allowing the start of supportive care
while the sample is confirmed at a state lab.
BioMérieux is developing two tests, one that
generates a result within an hour that can be used outside of a lab and
the other for high-volume in-lab processing. Both may be available in
the next several weeks although regulatory sign-off could add to the
timeline.
Related diagnostic test makers: Thermo Fisher Scientific (TMO +2.8%), Roche (OTCQX:RHHBY +2%), Qiagen (QGEN +14.3%)
https://seekingalpha.com/news/3548128-race-in-full-stride-for-tests-to-identify-coronavirus-illnessEnlivex proposes use of Allocetra for critically ill COVID-19 patients
Thinly traded nano cap Enlivex Therapeutics (ENLV -5.6%) announces that
it, along with the Head of Israel Economic and Commercial Mission to
South Korea, has submitted a proposal to South Korean authorities
regarding the potential use of Allocetra in COVID-19 patients
hospitalized in ICUs and suffering from organ dysfunction/failure.
The company is developing Allocetra,
an immunotherapy designed to avert cytokine storms (excessive and
life-threatening immune responses) and restore immune balance, for the
potential treatment of patients with organ failure due to sepsis.
Investors’ reaction to yesterday’s announced equity offering appears to be carrying over today.
https://seekingalpha.com/news/3548102-enlivex-proposes-use-of-allocetra-for-critically-ill-covidminus-19-patientsGuide to coronavirus drugs and vaccines in development
In the months since the novel coronavirus rose from a regional crisis
to a global threat, drug makers large and small have scrambled to
advance their best ideas for thwarting a pandemic.
Some are repurposing old antivirals. Some are mobilizing tried-and-true technologies, and others are pressing forward with futuristic approaches to human medicine.
Here’s a guide to some of the most talked-about efforts to treat or prevent coronavirus infection, with details on the science, history, and timeline for each endeavor.
Stage: Phase 3
Gilead’s remdesivir, an intravenous treatment, has already been used to treat one infected patient in the U.S. and will soon be deployed in a pair of large, late-stage studies in Asia. Later this month, Gilead will recruit about 1,000 patients diagnosed with the coronavirus to determine whether multiple doses of remdesivir can reverse the infection. The primary goals are reducing fever and helping patients get out of the hospital within two weeks. The drug, which previously failed in a study on Ebola virus, is also being studied in smaller trials in China and the U.S.
Stage: Phase 1
Moderna set a drug industry record with mRNA-1273, a vaccine candidate identified just 42 days after the novel coronavirus was sequenced. The company is working with the National Institutes of Health on a healthy-volunteer study expected to begin next month. If mRNA-1273 proves itself to be safe, the two organizations will enroll hundreds more patients to determine whether the vaccine protects against infection. Moderna’s product is a synthetic strand of messenger RNA, or mRNA, designed to convince bodily cells to produce antibodies against the virus. The company, founded in 2010, is yet to win Food and Drug Administration approval for any of its mRNA medicines.
Stage: Preclinical
Like Moderna, CureVac uses man-made mRNA to spur the production of proteins. And, like Moderna, it got a grant from the nonprofit Coalition for Epidemic Preparedness Innovations to apply its technology to coronavirus. CureVac has said it expects to have a candidate ready for human testing within a few months. The company is also working with CEPI on a mobile mRNA manufacturing technology, one that would theoretically allow health care workers to rapidly produce vaccines to respond at the site of an outbreak.
Stage: Preclinical
GlaxoSmithKline, one of the world’s largest vaccine manufacturers, is lending its technology to a Chinese biotech firm at work on a coronavirus vaccine. Under an agreement signed last month, GSK is providing its proprietary adjuvants — compounds that enhance the effectiveness of vaccines — to Clover Biopharmaceuticals, a privately held company based in Chengdu. Clover’s approach involves injecting proteins that spur an immune response, thereby priming the body to resist infection. The company has not said when it expects to advance into human testing.
Stage: Preclinical
Inovio has spent the last four decades working to turn DNA into medicine, and the company believes its technology could quickly generate a vaccine for the novel coronavirus. Working with CEPI grant money, Inovio has come up with a DNA vaccine it believes can generate protective antibodies and keep patients from infection. The company has partnered with a Chinese manufacturer, Beijing Advaccine Biotechnology, and is working through preclinical development with a candidate called INO-4800. The company expects to progress into clinical trials later this year.
Stage: Preclinical
Johnson & Johnson, which has in the past responded to outbreaks of the Ebola and Zika viruses, is taking a multipronged approach to the coronavirus. The company is in the early days of developing a vaccine that would introduce patients to a deactivated version of the virus, triggering an immune response without causing infection. At the same time, J&J is working with the federal Biomedical Advanced Research and Development Authority on potential treatments for patients who are already infected, a process that includes investigating whether any of its older medicines might work against the coronavirus.
Stage: Preclinical
Regeneron has grown into a $50 billion business based on its ability to craft human antibodies out of genetically engineered mice. Now it’s tapping that technology in hopes of treating coronavirus. The company is immunizing its antibody-generating mice with a harmless analog of the novel coronavirus, generating potential treatments for the infection. The most potent antibody results will go into animal testing, and if everything goes according to plan, Regeneron will be ready for human testing by late summer. The last time Regeneron embarked on this process, during the Ebola outbreak of 2015, it came up with an antibody cocktail that roughly doubled survival rates for treated patients.
Stage: Preclinical
Sanofi, which has successfully developed vaccines for yellow fever and diphtheria, is working with BARDA on an answer to the coronavirus. Sanofi’s approach involves taking some of the coronavirus’s DNA and mixing it with genetic material from a harmless virus, creating a chimera that can prime the immune system without making patients sick. Sanofi expects to have a vaccine candidate to test in the lab within six months and could be ready to test a vaccine in people within a year to 18 months. Approval would likely be at least three years away, the company said. Sanofi previously put its technology to work against SARS, a close relative of the novel virus.
Stage: Preclinical
Vir Biotechnology, a company focused on infectious disease, has isolated antibodies from people who survived SARS, a viral relative of the novel coronavirus, and is working to determine whether they might treat the infection. Teaming up with Chinese pharma contractor WuXi Biologics, the San Francisco-based Vir is in the early stages of development and hasn’t specified when it expects to have products ready for human testing. Vir’s CEO, Biogen veteran George Scangos, is also coordinating the trade group BIO’s response to the coronavirus outbreak.
Some are repurposing old antivirals. Some are mobilizing tried-and-true technologies, and others are pressing forward with futuristic approaches to human medicine.
Here’s a guide to some of the most talked-about efforts to treat or prevent coronavirus infection, with details on the science, history, and timeline for each endeavor.
Gilead Sciences
Approach: TreatmentStage: Phase 3
Gilead’s remdesivir, an intravenous treatment, has already been used to treat one infected patient in the U.S. and will soon be deployed in a pair of large, late-stage studies in Asia. Later this month, Gilead will recruit about 1,000 patients diagnosed with the coronavirus to determine whether multiple doses of remdesivir can reverse the infection. The primary goals are reducing fever and helping patients get out of the hospital within two weeks. The drug, which previously failed in a study on Ebola virus, is also being studied in smaller trials in China and the U.S.
Moderna Therapeutics
Approach: VaccineStage: Phase 1
Moderna set a drug industry record with mRNA-1273, a vaccine candidate identified just 42 days after the novel coronavirus was sequenced. The company is working with the National Institutes of Health on a healthy-volunteer study expected to begin next month. If mRNA-1273 proves itself to be safe, the two organizations will enroll hundreds more patients to determine whether the vaccine protects against infection. Moderna’s product is a synthetic strand of messenger RNA, or mRNA, designed to convince bodily cells to produce antibodies against the virus. The company, founded in 2010, is yet to win Food and Drug Administration approval for any of its mRNA medicines.
CureVac
Approach: VaccineStage: Preclinical
Like Moderna, CureVac uses man-made mRNA to spur the production of proteins. And, like Moderna, it got a grant from the nonprofit Coalition for Epidemic Preparedness Innovations to apply its technology to coronavirus. CureVac has said it expects to have a candidate ready for human testing within a few months. The company is also working with CEPI on a mobile mRNA manufacturing technology, one that would theoretically allow health care workers to rapidly produce vaccines to respond at the site of an outbreak.
GlaxoSmithKline
Approach: VaccineStage: Preclinical
GlaxoSmithKline, one of the world’s largest vaccine manufacturers, is lending its technology to a Chinese biotech firm at work on a coronavirus vaccine. Under an agreement signed last month, GSK is providing its proprietary adjuvants — compounds that enhance the effectiveness of vaccines — to Clover Biopharmaceuticals, a privately held company based in Chengdu. Clover’s approach involves injecting proteins that spur an immune response, thereby priming the body to resist infection. The company has not said when it expects to advance into human testing.
Inovio Pharmaceuticals
Approach: VaccineStage: Preclinical
Inovio has spent the last four decades working to turn DNA into medicine, and the company believes its technology could quickly generate a vaccine for the novel coronavirus. Working with CEPI grant money, Inovio has come up with a DNA vaccine it believes can generate protective antibodies and keep patients from infection. The company has partnered with a Chinese manufacturer, Beijing Advaccine Biotechnology, and is working through preclinical development with a candidate called INO-4800. The company expects to progress into clinical trials later this year.
Johnson & Johnson
Approach: Vaccine and treatmentStage: Preclinical
Johnson & Johnson, which has in the past responded to outbreaks of the Ebola and Zika viruses, is taking a multipronged approach to the coronavirus. The company is in the early days of developing a vaccine that would introduce patients to a deactivated version of the virus, triggering an immune response without causing infection. At the same time, J&J is working with the federal Biomedical Advanced Research and Development Authority on potential treatments for patients who are already infected, a process that includes investigating whether any of its older medicines might work against the coronavirus.
Regeneron Pharmaceuticals
Approach: TreatmentStage: Preclinical
Regeneron has grown into a $50 billion business based on its ability to craft human antibodies out of genetically engineered mice. Now it’s tapping that technology in hopes of treating coronavirus. The company is immunizing its antibody-generating mice with a harmless analog of the novel coronavirus, generating potential treatments for the infection. The most potent antibody results will go into animal testing, and if everything goes according to plan, Regeneron will be ready for human testing by late summer. The last time Regeneron embarked on this process, during the Ebola outbreak of 2015, it came up with an antibody cocktail that roughly doubled survival rates for treated patients.
Sanofi
Approach: VaccineStage: Preclinical
Sanofi, which has successfully developed vaccines for yellow fever and diphtheria, is working with BARDA on an answer to the coronavirus. Sanofi’s approach involves taking some of the coronavirus’s DNA and mixing it with genetic material from a harmless virus, creating a chimera that can prime the immune system without making patients sick. Sanofi expects to have a vaccine candidate to test in the lab within six months and could be ready to test a vaccine in people within a year to 18 months. Approval would likely be at least three years away, the company said. Sanofi previously put its technology to work against SARS, a close relative of the novel virus.
Vir Biotechnology
Approach: TreatmentStage: Preclinical
Vir Biotechnology, a company focused on infectious disease, has isolated antibodies from people who survived SARS, a viral relative of the novel coronavirus, and is working to determine whether they might treat the infection. Teaming up with Chinese pharma contractor WuXi Biologics, the San Francisco-based Vir is in the early stages of development and hasn’t specified when it expects to have products ready for human testing. Vir’s CEO, Biogen veteran George Scangos, is also coordinating the trade group BIO’s response to the coronavirus outbreak.
A detailed guide to the coronavirus drugs and vaccines in development
Who is getting sick, and how sick? Coronavirus risk by demographic factors
The new coronavirus
is not an equal-opportunity killer: Being elderly and having other
illnesses, for instance, greatly increases the risk of dying from the
disease the virus causes, Covid-19. It’s also possible being male could
put you at increased risk.
For both medical and public health reasons, researchers want to figure out who’s most at risk of being infected and who’s most at risk of developing severe or even lethal illness. With that kind of information, clinicians would know whom to treat more aggressively, government officials would have a better idea of steps to take, and everyone would know whether they need to take special, additional precautions.
Here’s what research has shown three months into the outbreak:
Old and young
The vast majority of cases in China — 87% — were in people ages 30 to 79, the China Center for Disease Control reported last month based on data from all 72,314 of those diagnosed with Covid-19 as of Feb. 11. That probably reflects something about biology more than lifestyle, such as being in frequent contact with other people. Teens and people in their 20s also encounter many others, at school and work and on public transit, yet they don’t seem to be contracting the disease at significant rates: Only 8.1% of cases were 20-somethings, 1.2% were teens, and 0.9% were 9 or younger. The World Health Organization mission to China found that 78% of the cases reported as of Feb. 20 were in people ages 30 to 69.
The death toll skews old even more strongly. Overall, China CDC found, 2.3% of confirmed cases died. But the fatality rate was 14.8% in people 80 or older, likely reflecting the presence of other diseases, a weaker immune system, or simply worse overall health. By contrast, the fatality rate was 1.3% in 50-somethings, 0.4% in 40-somethings, and 0.2% in people 10 to 39.
The age-related death risk probably reflects the strength, or weakness, of the respiratory system. About half of the 109 Covid-19 patients (ages 22 to 94) treated at Central Hospital of Wuhan, researchers there reported, developed acute respiratory distress syndrome (ARDS), in which fluid builds up in the small air sacs of the lungs. That restricts how much air the lungs can take in, reducing the oxygen supply to vital organs, sometimes fatally; half of the ARDS patients died, compared to 9% of patients who did not develop the syndrome.
The ARDS patients had an average age of 61, compared to an average age of 49 for those who did not develop ARDS. Elderly patients “were more likely to develop ARDS,” the researchers wrote, suggesting how age can make Covid-19 more severe and even fatal: age increases the risk that the respiratory system will basically shut down under viral assault.
Youth, in contrast, seems to be protective. The WHO mission reported a relatively low incidence in people under 18, who made up only 2.4% of all reported cases. In fact, through mid-January, zero children in Wuhan, the epicenter of the outbreak, had contracted Covid-19. It’s not clear whether that’s because children do not show signs of illness even if infected.
Even cases among children and teens aged 10 to 19 are rare. As of Feb. 11 there were 549 cases in that age group, 1.2% of the total, China CDC found. Only one had died.
One intriguing explanation for the apparent resilience of youth: in regions near Hubei province, young children seem especially likely to be exposed to other coronaviruses, scientists in China reported in 2018. That might have given them at least partial immunity to this one.
Men and women
The effect of sex on susceptibility to Covid-19 is less clear than the age effect, but preliminary data suggest men might be more susceptible. China CDC found that 106 men had the disease for every 100 women, while the WHO mission found that men make up 51% of cases. A study of 1,099 Covid-19 patients in Wuhan through Jan. 29 found a greater imbalance: 58% were male, the China Medical Treatment Expert Group for Covid-19 reported last week in the New England Journal of Medicine.
It’s possible the apparent sex imbalance reflects patterns of travel and contacts that make men more likely to be exposed to carriers of the virus, not any inherent biological differences. It’s also possible the apparent worse disease severity in men could skew the data. Among hospitalized patients, there is “a slight predominance of men,” U.S. researchers wrote last week in the Journal of the American Association. If the virus hits men harder than women, health care systems will see, test, and count more men.
To determine if there are sex differences in susceptibility to infection would require an unethical experiment: expose 1,000 otherwise similar men and women to the virus and see who gets sick.
The difference is fatality rates, however, is real: 1.7% for women and 2.8% for men, China CDC reported.
Sick or healthy
The male-female difference in fatality rates, and perhaps in reported incidence, may arise from differences in underlying health. People with pre-existing illness are more likely to get seriously ill from Covid-19, and men have a higher incidence of such chronic illnesses as cardiovascular disease.
In the first large study of the effect of underlying illness, researchers in China analyzed 1,590 patients from throughout the country with laboratory-confirmed disease. They calculated how “co-morbidities” — existing illnesses — affected the risk of being admitted to intensive care, being put on a ventilator, or dying.
After taking into account the patients’ ages and smoking status, the researchers found that the 399 patients with at least one additional disease (including cardiovascular diseases, diabetes, hepatitis B, chronic obstructive pulmonary disease, chronic kidney diseases, and cancer) had a 79% greater chance of requiring intensive care or a respirator or both, or of dying, they reported last week in a paper posted to medRxiv, a preprint site that posts research before it has been peer-reviewed. The 130 with two or more additional diseases had 2.5 times the risk of any of those outcomes.
That fits with what’s known about other respiratory viruses. People with a single co-morbidity who catch avian flu (H7N9) are 3.4 times more likely than otherwise-healthy flu patients to require ventilators and other intensive care. SARS and MERS, which are also caused by coronaviruses, are more severe in patients with underlying illnesses, too.
Breaking down the Covid-19 risk with the most common co-morbidities, the scientists found that cancer raises the risk 3.5-fold, COPD 2.6-fold, and diabetes and hypertension by about 60%. Because it isn’t unusual for someone to have an underlying disease (especially diabetes and hypertension) but not know it, the last figure is likely an underestimate.
Co-morbidities also raise the risk of dying from Covid-19. China CDC’s analysis of 44,672 patients found that the fatality rate in patients who reported no other health conditions was 0.9%. It was 10.5% for those with cardiovascular disease, 7.3% for those with diabetes, 6.3% for people with chronic respiratory diseases such as COPD, 6.0% for people with hypertension, and 5.6% for those with cancer.
Underlying disease might change the course of Covid-19. During the height of the epidemic in Wuhan, 37 of 230 patients receiving dialysis for kidney failure at Remnin Hospital developed the disease. Even though none were sick enough to require intensive care or a mechanical ventilator, six of them died, for a very high fatality rate of 16%. Oddly, however, none of the six died of pneumonia, Remnin researchers reported. Instead, the causes of death were heart disease, stroke, and high blood levels of potassium (a result of kidney failure). The high fatality rate of Covid-19 in already-sick people might result not from the virus but from an exacerbation of existing disease.
About 60% of U.S. adults have at least one underlying health condition, Tom Frieden, former director of the U.S. Centers for Disease Control and Prevention, told reporters on Monday.
Pregnancy
In early February, Chinese state media reported that a woman infected with the virus gave birth to a baby who later tested positive for it. Newborns might become infected because of close proximity to a patient, like anyone else, but the case raised fears that a pregnant woman can transmit the virus to her fetus via the placenta.
Only one small study has investigated such “vertical transmission.” Scientists at Wuhan University found that, of nine pregnant patients infected with the virus (all had a caesarean section) in their third trimester, none seemed to pass the virus to their babies, all of whom scored at the top of the Apgar scale of newborn health.
As for the mothers, “Covid-19 seems not to be especially severe in pregnant women, at least based on the small number in this study,” the scientists wrote. That was somewhat surprising because pregnancy suppresses the immune system (so it doesn’t attack the fetus); pregnant women are more susceptible to respiratory pathogens than non-pregnant women. Nevertheless, none of the nine women developed severe Covid-19 pneumonia.
It may be that immuno-suppression is actually helpful. Some of the most serious symptoms of Covid-19 result from an immune system on the rampage rather than a lethargic one, Chinese scientists found: An extreme immune response called cytokine storm, a flood of immune cells and the biochemicals they produce, tears through lung tissue.
For both medical and public health reasons, researchers want to figure out who’s most at risk of being infected and who’s most at risk of developing severe or even lethal illness. With that kind of information, clinicians would know whom to treat more aggressively, government officials would have a better idea of steps to take, and everyone would know whether they need to take special, additional precautions.
Here’s what research has shown three months into the outbreak:
The vast majority of cases in China — 87% — were in people ages 30 to 79, the China Center for Disease Control reported last month based on data from all 72,314 of those diagnosed with Covid-19 as of Feb. 11. That probably reflects something about biology more than lifestyle, such as being in frequent contact with other people. Teens and people in their 20s also encounter many others, at school and work and on public transit, yet they don’t seem to be contracting the disease at significant rates: Only 8.1% of cases were 20-somethings, 1.2% were teens, and 0.9% were 9 or younger. The World Health Organization mission to China found that 78% of the cases reported as of Feb. 20 were in people ages 30 to 69.
The death toll skews old even more strongly. Overall, China CDC found, 2.3% of confirmed cases died. But the fatality rate was 14.8% in people 80 or older, likely reflecting the presence of other diseases, a weaker immune system, or simply worse overall health. By contrast, the fatality rate was 1.3% in 50-somethings, 0.4% in 40-somethings, and 0.2% in people 10 to 39.
The age-related death risk probably reflects the strength, or weakness, of the respiratory system. About half of the 109 Covid-19 patients (ages 22 to 94) treated at Central Hospital of Wuhan, researchers there reported, developed acute respiratory distress syndrome (ARDS), in which fluid builds up in the small air sacs of the lungs. That restricts how much air the lungs can take in, reducing the oxygen supply to vital organs, sometimes fatally; half of the ARDS patients died, compared to 9% of patients who did not develop the syndrome.
The ARDS patients had an average age of 61, compared to an average age of 49 for those who did not develop ARDS. Elderly patients “were more likely to develop ARDS,” the researchers wrote, suggesting how age can make Covid-19 more severe and even fatal: age increases the risk that the respiratory system will basically shut down under viral assault.
Youth, in contrast, seems to be protective. The WHO mission reported a relatively low incidence in people under 18, who made up only 2.4% of all reported cases. In fact, through mid-January, zero children in Wuhan, the epicenter of the outbreak, had contracted Covid-19. It’s not clear whether that’s because children do not show signs of illness even if infected.
Even cases among children and teens aged 10 to 19 are rare. As of Feb. 11 there were 549 cases in that age group, 1.2% of the total, China CDC found. Only one had died.
One intriguing explanation for the apparent resilience of youth: in regions near Hubei province, young children seem especially likely to be exposed to other coronaviruses, scientists in China reported in 2018. That might have given them at least partial immunity to this one.
Men and women
The effect of sex on susceptibility to Covid-19 is less clear than the age effect, but preliminary data suggest men might be more susceptible. China CDC found that 106 men had the disease for every 100 women, while the WHO mission found that men make up 51% of cases. A study of 1,099 Covid-19 patients in Wuhan through Jan. 29 found a greater imbalance: 58% were male, the China Medical Treatment Expert Group for Covid-19 reported last week in the New England Journal of Medicine.
It’s possible the apparent sex imbalance reflects patterns of travel and contacts that make men more likely to be exposed to carriers of the virus, not any inherent biological differences. It’s also possible the apparent worse disease severity in men could skew the data. Among hospitalized patients, there is “a slight predominance of men,” U.S. researchers wrote last week in the Journal of the American Association. If the virus hits men harder than women, health care systems will see, test, and count more men.
To determine if there are sex differences in susceptibility to infection would require an unethical experiment: expose 1,000 otherwise similar men and women to the virus and see who gets sick.
The difference is fatality rates, however, is real: 1.7% for women and 2.8% for men, China CDC reported.
Sick or healthy
The male-female difference in fatality rates, and perhaps in reported incidence, may arise from differences in underlying health. People with pre-existing illness are more likely to get seriously ill from Covid-19, and men have a higher incidence of such chronic illnesses as cardiovascular disease.
In the first large study of the effect of underlying illness, researchers in China analyzed 1,590 patients from throughout the country with laboratory-confirmed disease. They calculated how “co-morbidities” — existing illnesses — affected the risk of being admitted to intensive care, being put on a ventilator, or dying.
After taking into account the patients’ ages and smoking status, the researchers found that the 399 patients with at least one additional disease (including cardiovascular diseases, diabetes, hepatitis B, chronic obstructive pulmonary disease, chronic kidney diseases, and cancer) had a 79% greater chance of requiring intensive care or a respirator or both, or of dying, they reported last week in a paper posted to medRxiv, a preprint site that posts research before it has been peer-reviewed. The 130 with two or more additional diseases had 2.5 times the risk of any of those outcomes.
That fits with what’s known about other respiratory viruses. People with a single co-morbidity who catch avian flu (H7N9) are 3.4 times more likely than otherwise-healthy flu patients to require ventilators and other intensive care. SARS and MERS, which are also caused by coronaviruses, are more severe in patients with underlying illnesses, too.
Breaking down the Covid-19 risk with the most common co-morbidities, the scientists found that cancer raises the risk 3.5-fold, COPD 2.6-fold, and diabetes and hypertension by about 60%. Because it isn’t unusual for someone to have an underlying disease (especially diabetes and hypertension) but not know it, the last figure is likely an underestimate.
Co-morbidities also raise the risk of dying from Covid-19. China CDC’s analysis of 44,672 patients found that the fatality rate in patients who reported no other health conditions was 0.9%. It was 10.5% for those with cardiovascular disease, 7.3% for those with diabetes, 6.3% for people with chronic respiratory diseases such as COPD, 6.0% for people with hypertension, and 5.6% for those with cancer.
Underlying disease might change the course of Covid-19. During the height of the epidemic in Wuhan, 37 of 230 patients receiving dialysis for kidney failure at Remnin Hospital developed the disease. Even though none were sick enough to require intensive care or a mechanical ventilator, six of them died, for a very high fatality rate of 16%. Oddly, however, none of the six died of pneumonia, Remnin researchers reported. Instead, the causes of death were heart disease, stroke, and high blood levels of potassium (a result of kidney failure). The high fatality rate of Covid-19 in already-sick people might result not from the virus but from an exacerbation of existing disease.
About 60% of U.S. adults have at least one underlying health condition, Tom Frieden, former director of the U.S. Centers for Disease Control and Prevention, told reporters on Monday.
Pregnancy
In early February, Chinese state media reported that a woman infected with the virus gave birth to a baby who later tested positive for it. Newborns might become infected because of close proximity to a patient, like anyone else, but the case raised fears that a pregnant woman can transmit the virus to her fetus via the placenta.
Only one small study has investigated such “vertical transmission.” Scientists at Wuhan University found that, of nine pregnant patients infected with the virus (all had a caesarean section) in their third trimester, none seemed to pass the virus to their babies, all of whom scored at the top of the Apgar scale of newborn health.
As for the mothers, “Covid-19 seems not to be especially severe in pregnant women, at least based on the small number in this study,” the scientists wrote. That was somewhat surprising because pregnancy suppresses the immune system (so it doesn’t attack the fetus); pregnant women are more susceptible to respiratory pathogens than non-pregnant women. Nevertheless, none of the nine women developed severe Covid-19 pneumonia.
It may be that immuno-suppression is actually helpful. Some of the most serious symptoms of Covid-19 result from an immune system on the rampage rather than a lethargic one, Chinese scientists found: An extreme immune response called cytokine storm, a flood of immune cells and the biochemicals they produce, tears through lung tissue.
Who is getting sick, and how sick? A breakdown of coronavirus risk by demographic factors
Trump’s tone toward pharma shifts, eying drug makers’ aid in coronavirus response
President Trump had billed the meeting with pharmaceutical executives
as a scolding waiting to happen. The gathering was intended to pressure
the industry to bring drug prices “way down,” he said on Friday,
suggesting it had only later morphed into a “convenient” opportunity to
discuss the development of a coronavirus vaccine.
But seated across from 10 pharmaceutical executives in the Cabinet Room on Monday, Trump’s long-simmering contempt for the drug industry melted away. Trump told executives from Gilead, Johnson & Johnson, and Pfizer that they worked for a “great company.” He affectionately referred to Leonard Schleifer, the CEO of Regeneron, as “Lenny.” At one point, Trump referred to the assembled drug executives as “geniuses.”
The meeting signified a remarkable shift in Trump’s view of the pharmaceutical industry. After years of maintaining that drug companies charge “ripoff” prices, Trump appeared floored by the executives’ progress reports. He alternatingly praised CEOs and egged them on to lay out shorter and shorter timelines for bringing a vaccine to market. Trump, throughout the meeting, appeared so blown away by the drug companies’ claims that his deputies struggled to rein in his expectations.
“Like I’ve been telling you, Mr. President,” Tony Fauci, the director
of the National Institute on Allergy and Infectious Disease,
interjected at one point. “A year to a year and a half,” he said,
referring to the amount of time it will likely take to deploy an
effective vaccine to large populations.
Undeterred, Trump continued to ask various versions of the same question: “So what do you think in terms of timing?”
The executives largely told the president what he wanted to hear — that for both therapies and vaccines, companies could enter early testing within months, with the aim of reaching the market in time for peak season in a year’s time.
“It was: Tell us how fast you can go, but let’s keep safety in mind, and let’s make sure we create something manufacturable,” said Dan Menichella, CEO of CureVac, who was among the executives seated before Trump. The company, headquartered in Germany and Boston, uses messenger RNA to produce protective antibodies inside patients’ bodies, thereby preventing infection. CureVac expects to start testing its coronavirus vaccine in healthy volunteers by June, with further trials to come if the injection proves safe.
But even as Fauci and health secretary Alex Azar interrupted to caution the president that most therapies and vaccines were nowhere near ready, the president leaned into the executives’ positive spin.
“That’s very exciting,” Trump said at one point to Daniel O’Day, the CEO of the biotech giant Gilead Sciences, after he described progress on a therapy that could be used to mitigate coronavirus symptoms. “Get it done, Daniel. Don’t disappoint us.”
Fueling Trump’s optimism: When questioned by the president, drug company representatives often struggled to differentiate between projections for bringing drugs to late-stage trials and bringing them to market — so much so that Fauci became a de facto referee.
At one point, he responded to Stephane Bancel, the chief executive officer of Moderna, with a stern clarification: “You won’t have a vaccine — you’ll have a vaccine to go into testing.”
But he immediately pivoted to Regeneron’s Schleifer.
“But Lenny is talking about two months,” Trump replied. “I mean, I like the sound of a couple of months better.”
This time, it was Azar who interjected to clarify that Schleifer’s aggressive projection was for a phase I trial — not for a market-ready vaccine.
Only once did Trump admonish drug companies at all, in response to a question about whether the federal government would provide financial assistance to companies investing heavily on vaccine development.
“I think they’re so rich — I know the companies very well — some of them are so rich I think they could actually loan money to the federal government,” Trump said. “They don’t need money, they need time.”
Trump, who last week acknowledged he was “shocked” to learn the flu typically kills over 30,000 Americans annually, also displayed a surprising lack of scientific savvy. At one point, he asked the executives and federal researchers whether they believed existing flu vaccines could prove effective in halting COVID-19’s spread.
“You take a solid flu vaccine,” Trump asked, “you don’t think that would have an impact, or much of an impact, on corona?”
Fauci’s understated reply came quickly: “Probably not.”
The pharmaceutical industry gathering was the Trump administration’s latest effort to reassure the public that it is taking aggressive measures to prevent further coronavirus spread. During a press briefing later on Monday, Vice President Mike Pence argued that the risk to the general public remains low, noting that confirmed community spread is happening in limited areas in California and Washington state. Health Secretary Alex Azar said federal officials had spoken with local and state counterparts in those areas about mitigation strategies, including the potential of suspending school.
Pence, like Trump, also sang the drug industry’s praises following the meeting.
“Our pharmaceutical companies, which are recognized as the greatest in the world, have already formed a consortium to work together, to share information in the development of therapeutics and vaccines,” he said at a Monday press briefing with members of the White House coronavirus task force.
Pence, who will be visiting the National Institutes of Health and the CDC this week with the president, also said that authorities would start screening passengers coming to the United States from South Korea and Italy for signs of the virus, which include fever and cough. Federal authorities have already urged Americans not to travel to those two countries, as well as Iran and China.
Pence also highlighted the role that Ambassador Deborah Birx, a physician and public health expert, will play on the task force as its coronavirus response coordinator.
But seated across from 10 pharmaceutical executives in the Cabinet Room on Monday, Trump’s long-simmering contempt for the drug industry melted away. Trump told executives from Gilead, Johnson & Johnson, and Pfizer that they worked for a “great company.” He affectionately referred to Leonard Schleifer, the CEO of Regeneron, as “Lenny.” At one point, Trump referred to the assembled drug executives as “geniuses.”
The meeting signified a remarkable shift in Trump’s view of the pharmaceutical industry. After years of maintaining that drug companies charge “ripoff” prices, Trump appeared floored by the executives’ progress reports. He alternatingly praised CEOs and egged them on to lay out shorter and shorter timelines for bringing a vaccine to market. Trump, throughout the meeting, appeared so blown away by the drug companies’ claims that his deputies struggled to rein in his expectations.
Undeterred, Trump continued to ask various versions of the same question: “So what do you think in terms of timing?”
The executives largely told the president what he wanted to hear — that for both therapies and vaccines, companies could enter early testing within months, with the aim of reaching the market in time for peak season in a year’s time.
“It was: Tell us how fast you can go, but let’s keep safety in mind, and let’s make sure we create something manufacturable,” said Dan Menichella, CEO of CureVac, who was among the executives seated before Trump. The company, headquartered in Germany and Boston, uses messenger RNA to produce protective antibodies inside patients’ bodies, thereby preventing infection. CureVac expects to start testing its coronavirus vaccine in healthy volunteers by June, with further trials to come if the injection proves safe.
But even as Fauci and health secretary Alex Azar interrupted to caution the president that most therapies and vaccines were nowhere near ready, the president leaned into the executives’ positive spin.
“That’s very exciting,” Trump said at one point to Daniel O’Day, the CEO of the biotech giant Gilead Sciences, after he described progress on a therapy that could be used to mitigate coronavirus symptoms. “Get it done, Daniel. Don’t disappoint us.”
Fueling Trump’s optimism: When questioned by the president, drug company representatives often struggled to differentiate between projections for bringing drugs to late-stage trials and bringing them to market — so much so that Fauci became a de facto referee.
At one point, he responded to Stephane Bancel, the chief executive officer of Moderna, with a stern clarification: “You won’t have a vaccine — you’ll have a vaccine to go into testing.”
But he immediately pivoted to Regeneron’s Schleifer.
“But Lenny is talking about two months,” Trump replied. “I mean, I like the sound of a couple of months better.”
This time, it was Azar who interjected to clarify that Schleifer’s aggressive projection was for a phase I trial — not for a market-ready vaccine.
Only once did Trump admonish drug companies at all, in response to a question about whether the federal government would provide financial assistance to companies investing heavily on vaccine development.
“I think they’re so rich — I know the companies very well — some of them are so rich I think they could actually loan money to the federal government,” Trump said. “They don’t need money, they need time.”
Trump, who last week acknowledged he was “shocked” to learn the flu typically kills over 30,000 Americans annually, also displayed a surprising lack of scientific savvy. At one point, he asked the executives and federal researchers whether they believed existing flu vaccines could prove effective in halting COVID-19’s spread.
“You take a solid flu vaccine,” Trump asked, “you don’t think that would have an impact, or much of an impact, on corona?”
Fauci’s understated reply came quickly: “Probably not.”
The pharmaceutical industry gathering was the Trump administration’s latest effort to reassure the public that it is taking aggressive measures to prevent further coronavirus spread. During a press briefing later on Monday, Vice President Mike Pence argued that the risk to the general public remains low, noting that confirmed community spread is happening in limited areas in California and Washington state. Health Secretary Alex Azar said federal officials had spoken with local and state counterparts in those areas about mitigation strategies, including the potential of suspending school.
Pence, like Trump, also sang the drug industry’s praises following the meeting.
“Our pharmaceutical companies, which are recognized as the greatest in the world, have already formed a consortium to work together, to share information in the development of therapeutics and vaccines,” he said at a Monday press briefing with members of the White House coronavirus task force.
Pence, who will be visiting the National Institutes of Health and the CDC this week with the president, also said that authorities would start screening passengers coming to the United States from South Korea and Italy for signs of the virus, which include fever and cough. Federal authorities have already urged Americans not to travel to those two countries, as well as Iran and China.
Pence also highlighted the role that Ambassador Deborah Birx, a physician and public health expert, will play on the task force as its coronavirus response coordinator.
Trump’s tone toward pharma shifts, as he looks to drug makers to help with coronavirus response
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