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Sunday, August 2, 2020

Yale to lead trial of potential COVID-19 treatment apilimod

Yale School of Medicine and the biopharmaceutical firm AI Therapeutics have launched a multi-institutional clinical trial of a drug for treating COVID-19.
Known as LAM-002A (apilimod), the drug has a proven safety record. Preliminary research has shown it can block cellular entry and trafficking of the SARS-CoV-2 virus, the cause of COVID-19.
Previous trials involving more than 700 patients have shown LAM-002A to be safe for the treatment for autoimmune diseases and follicular lymphoma. The drug has received Fast Track Status and Orphan Drug Designation from the Food & Drug Administration for treatment of lymphoma.
The Yale Center for Clinical Investigation is now enrolling patients in a Phase II trial for the drug’s use as a COVID-19 treatment. The study is expected to enroll 142 newly diagnosed patients to test the safety and efficacy of the drug in reducing virus levels in infected individuals.
AI Therapeutics, a Guilford, Connecticut-based biopharmaceutical company formed by Yale alumnus Jonathan Rothberg, owns intellectual property rights to the drug.
A multi-institutional study published in Nature (PDF), which screened more than 13,000 existing drugs against two strains of the live SARS-CoV-2 virus, found LAM-002A to be the most effective in combatting the virus, including in lung cells infected with the virus. In another study in the journal Cell, another group of researchers independently showed that LAM-002A could combat SARS-CoV-2 infections in human lung cells.
AI Therapeutics’ unpublished data along with data recently published by the Scripps Research Institutesuggest that LAM-002A administered with remdesivir, already approved for treating COVID-19, can boost the effectiveness of the antiviral agent.
LAM-002A holds promise to be a powerful new therapy for COVID-19 patients to prevent progression of disease, hopefully avoiding the need for hospitalization” said Yale’s Murat Gunel, professor of neurosurgery and professor of genetics and neuroscience. Gunel serves as the chief scientific adviser to AI Therapeutics and has a financial interest in the company.
Gunel noted that if LAM-002A shows effectiveness in this phase, the trial could be expanded to assess whether it would help prevent the development of disease after exposure, particularly in high-risk populations, such as the elderly in nursing homes, health care and frontline workers, or people in underserved communities.
Charles S. Dela Cruz, associate professor of medicine and microbial pathogenesis and director of the Center for Pulmonary Infection Research at Yale University, will lead the study. Institutions in other areas of the country are expected to enroll patients soon.

Inflammation resolution: dual approach to averting cytokine storms in COVID-19?

Abstract

Severe coronavirus disease (COVID-19) is characterized by pulmonary hyper-inflammation and potentially life-threatening “cytokine storms”. Controlling the local and systemic inflammatory response in COVID-19 may be as important as anti-viral therapies. Endogenous lipid autacoid mediators, referred to as eicosanoids, play a critical role in the induction of inflammation and pro-inflammatory cytokine production. SARS-CoV-2 may trigger a cell death (“debris”)-induced “eicosanoid storm”, including prostaglandins and leukotrienes, which in turn initiates a robust inflammatory response. A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process with the discovery of novel endogenous specialized pro-resolving lipid autacoid mediators (SPMs), such as resolvins. Resolvins and other SPMs stimulate macrophage-mediated clearance of debris and counter pro-inflammatory cytokine production, a process called inflammation resolution. SPMs and their lipid precursors exhibit anti-viral activity at nanogram doses in the setting of influenza without being immunosuppressive. SPMs also promote anti-viral B cell antibodies and lymphocyte activity, highlighting their potential use in the treatment of COVID-19. Soluble epoxide hydrolase (sEH) inhibitors stabilize arachidonic acid-derived epoxyeicosatrienoic acids (EETs), which also stimulate inflammation resolution by promoting the production of pro-resolution mediators, activating anti-inflammatory processes, and preventing the cytokine storm. Both resolvins and EETs also attenuate pathological thrombosis and promote clot removal, which is emerging as a key pathology of COVID-19 infection. Thus, both SPMs and sEH inhibitors may promote the resolution of inflammation in COVID-19, thereby reducing acute respiratory distress syndrome (ARDS) and other life-threatening complications associated with robust viral-induced inflammation. While most COVID-19 clinical trials focus on “anti-viral” and “anti-inflammatory” strategies, stimulating inflammation resolution is a novel host-centric therapeutic avenue. Importantly, SPMs and sEH inhibitors are currently in clinical trials for other inflammatory diseases and could be rapidly translated for the management of COVID-19 via debris clearance and inflammatory cytokine suppression. Here, we discuss using pro-resolution mediators as a potential complement to current anti-viral strategies for COVID-19.

No SARS-CoV-2 cross-neutralization by IV immunoglobulins from pre-2020 plasma

Julia Schwaiger, Michael Karbiener, Claudia Aberham, Maria R. Farcet, Thomas R. Kreil

The risk of COVID-19 transmission in train passengers

Clinical Infectious Diseases, ciaa1057, https://doi.org/10.1093/cid/ciaa1057
Published:
29 July 2020

Abstract

Background
Train is a common mode of public transport across the globe; however, the risk of COVID-19 transmission among individual train passengers remains unclear.
Methods
We quantified the transmission risk of COVID-19 on high-speed train passengers using data from 2,334 index patients and 72,093 close contacts who had co-travel times of 0–8 hours from 19 December 2019 through 6 March 2020 in China. We analysed the spatial and temporal distribution of COVID-19 transmission among train passengers to elucidate the associations between infection, spatial distance, and co-travel time.
Results
The attack rate in train passengers on seats within a distance of 3 rows and 5 columns of the index patient varied from 0 to 10.3% (95% confidence interval [CI] 5.3% – 19.0%), with a mean of 0.32% (95%CI 0.29% – 0.37%). Passengers in seats on the same row as the index patient had an average attack rate of 1.5% (95%CI 1.3% – 1.8%), higher than that in other rows (0.14%, 95%CI 0.11% – 0.17%), with a relative risk (RR) of 11.2 (95%CI 8.6 –14.6). Travellers adjacent to the index patient had the highest attack rate (3.5%, 95%CI 2.9% – 4.3%) of COVID-19 infections (RR 18.0, 95%CI 13.9 – 23.4) among all seats. The attack rate decreased with increasing distance, but it increased with increasing co-travel time. The attack rate increased on average by 0.15% (p = 0.005) per hour of co-travel; for passengers at adjacent seats, this increase was 1.3% (p = 0.008), the highest among all seats considered.
Conclusions
COVID-19 has a high transmission risk among train passengers, but this risk shows significant differences with co-travel time and seat location. During disease outbreaks, when travelling on public transportation in confined spaces such as trains, measures should be taken to reduce the risk of transmission, including increasing seat distance, reducing passenger density, and use of personal hygiene protection.

Don’t Count on Lower Premiums Despite Pandemic-Driven Boon for Insurers

Numerous insurers across the country have announced plans to hike rates next year, though some have proposed cuts.


KEY TAKEAWAYS

The benefits reaped by health plans so far in the pandemic can be seen in strong second-quarter earnings and reduced spending on care.
UnitedHealth Group announced earlier this month that its net profit in the April-June quarter nearly doubled from the same period a year earlier.
Its medical spending plummeted from 83.1% of premium revenue to 70.2% over that period.
Anthem reported Wednesday that its net profit in the second quarter doubled from the same period in 2019, also on the back of plunging medical expenses.
UnitedHealth said it has provided $1.5 billion worth of financial support to consumers so far, including premium credits and cost-sharing waivers, and expects to pay out $1 billion in rebates.

When COVID-19 smacked the United States in March and April, health plans feared medical costs could skyrocket, jacking up premiums drastically in 2021, when millions of the newly unemployed might still be out of work.
But something else happened: Non-COVID care collapsed as hospitals emptied beds and shut down operating rooms to prepare for an expected onslaught of patients sickened by the coronavirus, while fear of contracting it kept people away from ERs, doctors’ offices and outpatient clinics. In many regions of the country, the onslaught did not come, and the billions of dollars lost by hospitals and physicians constituted huge savings for health plans, fattening their bottom lines.
But that doesn’t mean consumers will see lower premiums next year.
Numerous insurers across the country have announced plans to hike rates next year, though some have proposed cuts.
Peter Lee, executive director of Covered California, appeared skeptical about premium reductions in the state’s Affordable Care Act exchange, which is likely to announce 2021 health plan rates next week.
“Would we like zero increases? Absolutely. Would we like them negative? Yeah — but not if that means you’re going to increase premiums in a year by 20%,” Lee said in an interview with California Healthline this week. “We’ve been leaning on them to do what we always lean on them to do, and this is to have the lowest possible rates where you won’t be on a rate roller coaster. We want health plans to price right — not to price artificially low or artificially high.”
Covered California provides coverage for about 1.5 million residents who buy their own insurance.
If the insurance exchanges in other states offer any guidance for Covered California, it is in the direction of moderate premium increases for 2021, though there is wide variation.
A KFF analysis last week of proposed 2021 rates in the exchanges of 10 states and the District of Columbia showed a median increase of 2.4%, with changes ranging from a hike of 31.8% by a health plan in New Mexico to a cut of 12% in Maryland. (Kaiser Health News, which produces California Healthline, is an editorially independent program of KFF.)
Among the roughly one-third of filings that stated how much COVID-19 added to premiums, the median was 2%, with estimates ranging from minus 1.2% at a plan in Maine to 8.6% at one in Michigan.
The proposed premiums for ACA marketplace plans do not affect job-based coverage, but they may indicate how the pandemic is affecting premiums generally.
The consensus among industry experts is that COVID-19 has generated little pressure for rate rises, and health plans should err on the side of moderation. But some fear that many insurers will hold onto the reserves they’ve built up, citing the possibility of widespread vaccinations and concerns that the care forgone in 2020 could rebound with a vengeance next year.
“The tendency of health plans, when they are faced with any degree of uncertainty, is to be very conservative and price for the worst-case scenario,” said Michael Johnson, an industry observer and critic who worked as an executive at Blue Shield of California from 2003 to 2015. “Actuaries are less likely to get fired if the plan prices too high than if the plan prices too low. But I think regulators really need to push back hard on that.”
Lee said all 11 insurers participating in the exchange this year will remain in 2021, and no new ones will be added to the mix, though some of the current carriers will extend their coverage geographically. Ninety percent of consumers who buy their own health insurance get subsidies from the federal government or the state to help pay their premiums.
In January, California became the first state to offer subsidies to middle-income people who make too much money to qualify for federal subsidies. The lion’s share of the state subsidies is earmarked for those who earn between 400% and 600% of the federal poverty level, or $51,040 to $76,560 a year for an individual and $104,800 to $157,200 for a family of four.
The rate proposals expected to be unveiled next week will be subject to scrutiny by state regulators before they are finalized. Sign-ups for the plans start Nov. 1 and run through Jan. 31. This year, the average Covered California rate increase statewide was 0.8%, the lowest since the exchange started providing coverage in 2014.
The benefits reaped by health plans so far in the pandemic can be seen in strong second-quarter earnings and reduced spending on care. UnitedHealth Group, the nation’s largest health insurer, announced earlier this month that its net profit in the April-June quarter nearly doubled from the same period a year earlier. Its medical spending plummeted from 83.1% of premium revenue to 70.2% over that period.
Anthem, the parent company of Blue Cross of California, reported Wednesday that its net profit in the second quarter doubled from the same period in 2019, also on the back of plunging medical expenses.
Anthem said it offered one-month premium credits ranging from 10% to 50% to enrollees in individual, employer and group dental policies — including its Blue Cross plans in California.
UnitedHealth said it has provided $1.5 billion worth of financial support to consumers so far, including premium credits and cost-sharing waivers, and expects to pay out $1 billion in rebates.
But UnitedHealth, which does not participate in Covered California, is seeking a rate increase of 13.8% in the New York exchange. Anthem, which covers about 80,000 people in Covered California, is planning rate hikes of 16.6% in Kentucky and 9.9% in Connecticut.
On the other hand, Kaiser Permanente, which covers more than one-third of Covered California enrollees, plans rate cuts in other states, ranging from 1% in Hawaii to 11% in Maryland. (Kaiser Health News, which produces California Healthline, is not affiliated with Kaiser Permanente.)
Lee downplayed the notion of a financial boon for California health plans, saying that, partly because of the use of telehealth, primary care has rebounded and the plans are paying for it. “So we don’t see this as being at this point a bonanza year for health plans,” he said. “Rather, it’s a year in which there are lessons learned for how we can deliver care in a pandemic.”
Still, the health plans are in a far stronger position than they had feared earlier this year.
In March, Covered California released a study showing that COVID-19’s impact on 2021 premiums for individuals and employers could range from an increase of 4% to more than 40%. But less than three months later, projections commissioned by the industry’s national advocacy group, America’s Health Insurance Plans, showed that even in the worst-case scenario of a 60% COVID infection rate — far above where it stands now — the pandemic would increase medical costs in 2020 and 2021 by 6% at most, and could even decrease them.
That moderate effect is largely attributable to what Katherine Hempstead, a senior policy adviser at the Robert Wood Johnson Foundation, called “a kind of yin and yang: If you have a lot of COVID, you don’t have a lot of other healthcare spending.”
Independent of the course the pandemic takes, emergency room and outpatient visits still lag behind pre-COVID levels and will probably continue to do so next year, to the continued benefit of insurers, predicted Glenn Melnick, a professor of healthcare finance at the University of Southern California’s Sol Price School of Public Policy. That could be good news for consumers, he said, potentially leading to lower premium increases or even reductions next year.
On the other hand, hospitals and doctors have lost money, and the ones whose contracts with health plans are up for renewal will be looking to make up those losses, Melnick said.
“Providers could be asking for 20-25% increases next year,” he said, “and if they’ve got market power, they can make it stick.”

Siemens Healthineers near $15B deal for Varian

August 2, 2020

Siemens Healthineers (OTC:SEMHF) is in advanced talks to buy Varian Medical Systems (NYSE:VAR) in a deal that could value the company at ~$15B, Bloomberg reports.
Varian shares have edged 0.5% higher this year, while Healthineers, a spinoff from Siemens in 2018, has risen 2.7% YTD.
Healthineers said two months ago its coronavirus antibody test received Emergency Use Authorization from the FDA, which would allow users to identify recent or prior infection.

Saturday, August 1, 2020

Two thirds of UK firms ‘fully operational’ after COVID, survey says

Two thirds of British businesses say they are now “fully operational” after the coronavirus lockdown, up from half in June, according to a survey on Sunday.
A further 21% of the firms, polled in the first half of July by the Confederation of British Industry (CBI), said they were partly operational with some premises still closed.
“With businesses gradually reopening, this month’s data seems to indicate a turning point for the economy,” said Alpesh Paleja, an economist for CBI, one of Britain’s main business lobby groups.
But many firms, especially those in consumer-facing sectors, remained in “acute financial distress”, he added.
Britain’s lockdown has been slowly lifting since May, with the last major change on July 4 when hotels, pubs and restaurants were allowed to reopen.
However, on Friday Prime Minister Boris Johnson said he was postponing further relaxation, which would have helped some arts and entertainment venues, due to rising cases.
Businesses on average said they were operating at 85% of usual capacity due to social distancing, compared with 72% when a stricter rule generally requiring two metres of distance was in force.
Lack of demand from customers continued to be businesses’ most common challenge to resuming normal operations, the CBI said. More than two thirds of firms named it as a barrier to normal operations, down slightly from three quarters in June.
The Bank of England is due to set out new quarterly forecasts on Thursday, as different sectors of the economy recover at different rates from the unprecedented economic damage.
Whether the main barrier to growth is lack of consumer demand, or businesses’ difficulties meeting it, will be key to the central bank’s decisions on stimulus later this year.