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Wednesday, July 15, 2020

Merck & Co’s CEO has doubts over fast COVID-19 vaccine development

Merck & Co’s CEO Kenneth Frazier has warned that the many COVID-19 vaccines under development are not guaranteed to work, adding that it may be too optimistic to expect one to be approved and ready by year-end. 
According to Reuters and other news outlets, Frazier said that those who expect a vaccine before year end are doing a “grave disservice to the public”. 
The reports cited comments made by Frazier to the subscription-only publication the Harvard Business Review. 
Frazier warned that the potential vaccines may not be of sufficient quality to be rapidly deployed in large numbers of people, according to the interview published on Monday. 
“If you’re going to use a vaccine on billions of people, you better know what that vaccine does.” 
Frazier’s comments followed comments from an unnamed US official who told Reuters that a vaccine will be in production and manufacturing in between four and six weeks’ time “by the end of summer”. 
As part of the Trump administration’s Operation Warp Speed vaccine development programme, the US government has given grants for vaccines ranging from several hundred million dollars to over $1 billion to Johnson & Johnson, Moderna, AstraZeneca and Novovax. 
The programme aims to make 300 million vaccine doses by the end of 2021. 
Frazier said some previous vaccines “not only didn’t confer protection, but actually helped the virus invade the cell, because it was incomplete in terms of its immunogenic properties.” 
“So we have to be very careful.” 
Frazier is one of only four black CEOs of Fortune 500 companies, and he expressed concern in the interview about the higher death rates seen among non-white people. 
He said this had highlighted “huge structural elements of racism that have existed in this country (the US) for a long time.” 
US companies must get rid of processes and systems that prevent black employees from advancing, Frazier added. 
He said: “At the end of the day, if you’re complacent with the status quo, you’re complicit in the racism that the status quo hides.” 
US-based Merck & Co  is behind its rivals with its COVID-19 vaccine, which is one of 140 in preclinical development. 
The World Health Organization has been keeping tabs on the race to develop a vaccine against COVID-19 and says there are now 23 in clinical development. 
China’s Sinovac is top of the list, closely followed by AstraZeneca and the University of Oxford, with both of these vaccines fast-tracked into phase 3 development.

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FDA Ad Com backs Mallinckrodt’s terlipressin in close vote

The FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 8-7 that the benefits of Mallinckrodt’s (MNK +11.1%) terlipressin outweigh the risks for the treatment of hepatorenal syndrome type 1.

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COVID-19 risks ‘moderate while flying’

The WSJ reports that airlines and airplane makers are mounting a major campaign aimed at reassuring potential passengers wary of contracting COVID-19 that it is safe to fly.
At present, flying is not as safe as the airlines claim but it is safer than many people think, concludes the Journal‘s Scott McCartney.
One of the public’s fears is the perception that air is repeatedly recycled in the cabin during flight, potentially providing ample opportunities to inhale SARS-CoV-2 viruses that are floating about. According to Airbus Americas’ VP for R&D Amanda Simpson, the cabin is not a sealed tube. Fresh air from outside the plane is constantly infused with the old and all of it is “significantly” filtered which, she says, makes airplane air safer from the coronavirus than many other indoor public settings such as restaurants and office buildings. Wearing a mask and using hand sanitizer after trips to the lavatory further improve safety.
A recent study conducted for the International Air Transport Association revealed that 65% of respondents listed sitting next to someone that might be infected is their top concern. Using the restroom was second.
A computer simulation study done in Germany showed that the highest risk for COVID-19 infection is during boarding and exit since people are closer together.
Airplane disease transmission expert Mark Gendreau, chief medical officer at Beverly and Addison Gilbert hospitals in Massachusetts, says, “The overall risk, I think right now, I would put it at moderate.”
The public relations campaign needs to be a good one. Airlines are faced with a significant long-term drop in passenger miles otherwise.
Selected tickers: Delta Air Lines (DAL +5.3%), Southwest Airlines (LUV +5.3%), American Airlines Group (AAL +8.9%), United Airlines (UAL +9.3%), JetBlue (JBLU +7.6%), Alaska Air Group (ALK +6.2%), Spirit Airlines (SAVE +8.2%), Boeing (BA +2.9%), Airbus SE (OTCPK:EADSF +7.3%)

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Sobering Data on Risks of Short-Term Oral Corticosteroids

Corticosteroid bursts as short as 2 weeks or less were still linked to severe adverse events among relatively healthy users, according to a large study from Taiwan.
For people taking oral steroids over a median 3 days, the risk of such events was elevated in the 5-30 days after steroid therapy initiation compared with the reference period (5-90 days before initiation):
  • GI bleeding: 27.1 per 1,000 person-years (incidence rate ratio 1.80, 95% CI 1.75-1.84)
  • Sepsis: 1.5 per 1,000 person-years (IRR 1.99, 95% CI 1.70-2.32)
  • Heart failure: 1.3 per 1,000 person-years (IRR 2.37, 95% CI 2.13-2.63)
Patients with and without comorbid conditions experienced similar increases in adverse events following their steroid bursts. While risk attenuated somewhat during days 31-90, it remained elevated, reported Tsung-Chieh Yao, MD, PhD, of Chang Gung Memorial Hospital in Taoyuan, and colleagues in the Annals of Internal Medicine.
“Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear,” according to the investigators.
Notably, one corticosteroid that fits the bill is dexamethasone, now commonly used as a COVID-19 treatment. The NIH currently recommends dexamethasone 6 mg/day for up to 10 days in COVID-19 patients under mechanical ventilation (dexamethasone is not recommended for people not requiring supplemental oxygen).
“We are now learning that bursts as short as 3 days may increase risk for serious AEs [adverse events], even in young and healthy people. As providers, we must reflect on how and why we prescribe corticosteroids to develop strategies that prevent avoidable harms,” according to Beth Wallace, MD, and Akbar Waljee, MD, both of the VA Ann Arbor Healthcare System and Michigan Medicine.
“Although many providers already avoid corticosteroids in elderly patients and those with comorbid conditions, prescribing short bursts to ‘low-risk’ patients has generally been viewed as innocuous, even in cases where the benefit is unclear. However, Yao and colleagues provide evidence that this practice may risk serious harm, making it difficult to justify in cases where corticosteroid use lacks evidence of meaningful benefit,” they wrote in an accompanying editorial.
The self-controlled case series was based on national medical claims records. Included were adults, ages 20-64, covered by Taiwan’s National Health Insurance in 2013-2015.
Out of a population of more than 15.8 million, study authors identified 2,623,327 people who received a steroid burst during the study period. These individuals were age 38 on average, and 55.3% women. About 85% had no baseline comorbid conditions.
The most common indications for the steroid burst were skin disorders and respiratory tract infections.
Study authors acknowledged that they could not adjust for disease severity and major lifestyle factors such as alcohol use, smoking, and BMI. Their reliance on prescription data also meant they couldn’t tell if patients actually complied with oral corticosteroid therapy.
Furthermore, the exclusion of the elderly and younger populations also left room for underestimation of the risks of steroid bursts, they said.
“Medication-related risks for AEs can, of course, be outweighed by major treatment benefit. However, this study and prior work show that corticosteroid bursts are frequently prescribed for self-limited conditions, where evidence of benefit is lacking,” Wallace and Waljee noted.
“As we reflect on how to respond to these findings, it is useful to note the many parallels between use of corticosteroid bursts and that of other short-term medications, such as antibiotics and opiates. All of these treatments have well-defined indications but can cause net harm when used — as they frequently are — when evidence of benefit is low,” the editorialists emphasized.
Disclosures
The study was supported by National Health Research Institutes, Ministry of Science and Technology of Taiwan, Chang Gung Medical Foundation, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Yao, Wallace, and Waljee disclosed no relevant relationships with industry.
Primary Source
Annals of Internal Medicine
Source Reference: Yao T, et al “Association between oral corticosteroid bursts and severe adverse events” Ann Intern Med 2020; DOI: 10.7326/M20-0432.
Secondary Source
Annals of Internal Medicine
Source Reference: Wallace BI, Waljee AK “Burst case scenario: why shorter may not be any better when it comes to corticosteroids” Ann Intern Med 2020; DOI: 10.7326/M20-4234.

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CMS to deliver ‘point-of-care’ COVID-19 test kits to all nursing homes

“Every single” nursing home across the country will be given “point-of-care” COVID-19 tests by the administration starting next week, officials announced Tuesday.
Centers for Medicare & Medicaid Services Administrator Seema Verma announced the development at a press conference in Baton Rouge, LA, where Vice President Pence and others had traveled to meet with the governor and also promote school reopenings this fall.
The testing devices initially are to be given to 2,000 nursing homes next week, said Assistant Secretary of the Department of Health and Human Services Admiral Brett Giroir. He described them as “rapid on the spot, 20 tests per hour” devices and said that the goal is to get them to “every single of the 15,400 nursing homes within this country.”
Nursing homes would receive the devices in an order “ranked by Administrator Verma and her team,” as determined by the rate of the virus’ spread in the surrounding community, Giroir added. The administration has said lately that it has been focusing certain efforts on “hotspot” areas.
Verma noted that the point-of-care tests will be used for residents and workers.
“This is not an acquisition,” Giroir said. “This is not just writing a check and doing it. This has been the culmination of about two months of work, to develop the technology, increase the sensitivity of the test to make sure they’ll be highly protective. Of investments in technology, of regulatory flexibility with the FDA, to bring it all together.”
Giroir said the day’s announcement was a “really historic moment” and predicted that the deliveries would “save thousands of lives.”
The leader of the largest nursing home association in the United States called the testing announcement from Louisiana “welcome news for long-term care residents, staff and providers.”
“Repeated, ongoing testing is the only way we are going to beat this virus,” said American Health Care Association President and CEO Mark Parkinson. “Regular testing of nursing home and assisted living staff is a vital step in controlling the spread of COVID-19, but is not effective without obtaining timely test results. For nursing homes and assisted living communities to protect residents and staff, we need on-site testing with reliable and rapid results.”
Giroir separately told NPR in a report today that because testing has ramped up so quickly, the unprecedented demand has increased wait times for results from laboratories, often to about a week. The rise is something verified by results of an informal poll of hundreds of LeadingAge members Monday.
In a pair of poll questions posed to listeners on the LeadingAge daily coronavirus call, just about half (49%) reported longer recent wait times between testing and receiving results. The other responses were “no change” (29%) and “faster” (21%).
In terms of actual response times, the largest category was “2 to 5 days” (42%), followed by “5 to 7 days” (26%), “less than 48 hours” (17%) and “more than a week” (12%). The non-scientific polling did not measure geographic or provider-size mix.
Giroir told NPR that fast point-of-care tests can ease laboratories’ burdens, and possibly assist with faster reopenings of schools and businesses.
“Certainly by September, we expect to have 15 to 20 million point of care tests. That’s as many tests as we’re doing every month now,” Giroir said, adding that the administration wants to see 100 million tests per month happening then.
Critics of point-of-care testing have pointed out that error rates can be as high as 20%, meaning nearly one-fifth of all infections may be missed.

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SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS

Nature (2020)Cite this article

Abstract

Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections1. Little is known about the presence of pre-existing memory T cells in humans with the potential to recognize SARS-CoV-2. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in COVID-19 convalescents (n=36). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then showed that SARS-recovered patients (n=23) still possess long-lasting memory T cells reactive to SARS-NP 17 years after the 2003 outbreak, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37). SARS-CoV-2 T cells in uninfected donors exhibited a different pattern of immunodominance, frequently targeting the ORF-1-coded proteins NSP7 and 13 as well as the NP structural protein. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved amongst animal betacoranaviruses. Thus, infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing NP- and ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.

Author information

Author notes
  1. These authors contributed equally: Nina Le Bert, Anthony T. Tan

Affiliations

  1. Emerging Infectious Diseases Program, Duke-NUS Medical School, Singapore, Singapore
    Nina Le Bert, Anthony T. Tan, Kamini Kunasegaran, Christine Y. L. Tham, Morteza Hafezi, Adeline Chia, Melissa Hui Yen Chng, Meiyin Lin, Nicole Tan, Martin Linster, Wan Ni Chia, Lin-Fa Wang, Eng Eong Ooi, Jenny Guek-Hong Low & Antonio Bertoletti
  2. Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore, Singapore
    Meiyin Lin & Yee-Joo Tan
  3. National Center of Infectious Diseases, Singapore, Singapore
    Mark I-Cheng Chen
  4. Department of Infectious Diseases, Singapore General Hospital, Singapore, Singapore
    Shirin Kalimuddin & Jenny Guek-Hong Low
  5. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Paul Anantharajal Tambyah
  6. Division of Infectious Disease, University Medicine Cluster, National University Hospital, Singapore, Singapore
    Paul Anantharajal Tambyah
  7. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
    Yee-Joo Tan
  8. Singapore Immunology Network, A*STAR, Singapore, Singapore
    Antonio Bertoletti

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