Feeds:
Posts
Comments

Archive for the ‘Serology tests for coronavirus antibodies’ Category

Nir Hacohen and Marcia Goldberg, Researchers at MGH and the Broad Institute identify protein “signature” of severe COVID-19

Curator and Reporter: Aviva Lev-Ari, PhD, RN

Longitudinal proteomic analysis of plasma from patients with severe COVID-19 reveal patient survival-associated signatures, tissue-specific cell death, and cell-cell interactions

Open AccessPublished:April 30, 2021DOI:https://doi.org/10.1016/j.xcrm.2021.100287

Highlights

  • 16% of COVID-19 patients display an atypical low-inflammatory plasma proteome
  • Severe COVID-19 is associated with heterogeneous plasma proteomic responses
  • Death of virus-infected lung epithelial cells is a key feature of severe disease
  • Lung monocyte/macrophages drive T cell activation, together promoting epithelial damage

Summary

Mechanisms underlying severe COVID-19 disease remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune and non-immune proteins linked to COVID-19. Deconvolution of our plasma proteome data using published scRNAseq datasets reveals contributions from circulating immune and tissue cells. Sixteen percent of patients display reduced inflammation yet comparably poor outcomes. Comparison of patients who died to severely ill survivors identifies dynamic immune cell-derived and tissue-associated proteins associated with survival, including exocrine pancreatic proteases. Using derived tissue-specific and cell type-specific intracellular death signatures, cellular ACE2 expression, and our data, we infer whether organ damage resulted from direct or indirect effects of infection. We propose a model in which interactions among myeloid, epithelial, and T cells drive tissue damage. These datasets provide important insights and a rich resource for analysis of mechanisms of severe COVID-19 disease.

Graphical Abstract

Figure thumbnail fx1

Image Source: DOI: https://doi.org/10.1016/j.xcrm.2021.100287

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00115-4

The quest to identify mechanisms that might be contributing to death in COVID-19: Why do some patients die from this disease, while others — who appear to be just as ill do not?

Researchers at Massachusetts General Hospital (MGH) and the Broad Institute of MIT and Harvard have identified the protein “signature” of severe COVID-19

Interest was to develop methods for studying human immune responses to infections, which they had applied to the condition known as bacterial sepsis. The three agreed to tackle this new problem with the goal of understanding how the human immune system responds to SARS-CoV-2, the novel pathogen that causes COVID-19.

How scientists launched a study in days to probe COVID-19’s unpredictability

Collecting these specimens required a large team of collaborators from many departments, which worked overtime for five weeks to amass blood samples from 306 patients who tested positive for COVID-19, as well as from 78 patients with similar symptoms who tested negative for the coronavirus.

Alexandra-Chloé Villani

Credit : Alexandra-Chloé VillaniResearch associates at Mass General who worked countless hours to process blood samples for the COVID Acute Cohort Study (from left to right: Anna Gonye, Irena Gushterova, and Tom Lasalle)By Leah Eisenstadt

https://www.broadinstitute.org/news/how-scientists-launched-study-days-probe-covid-19%E2%80%99s-unpredictability

As the COVID-19 surge began in March, Mass General and Broad researchers worked around the clock to begin learning why some patients fare worse with the disease than others

Protein signatures in the blood

https://www.broadinstitute.org/news/researchers-identify-protein-%E2%80%9Csignature%E2%80%9D-severe-covid-19

The study found that most patients with COVID-19 have a consistent protein signature, regardless of disease severity; as would be expected, their bodies mount an immune response by producing proteins that attack the virus. “But we also found a small subset of patients with the disease who did not demonstrate the pro-inflammatory response that is typical of other COVID-19 patients,” Filbin said, yet these patients were just as likely as others to have severe disease. Filbin, who is also an assistant professor of emergency medicine at Harvard Medical School (HMS), noted that patients in this subset tended to be older people with chronic diseases, who likely had weakened immune systems.

Among other revelations, this showed that the most prevalent severity-associated protein, a pro-inflammatory protein called interleukin-6 (IL-6) rose steadily in patients who died, while it rose and then dropped in those with severe disease who survived. Early attempts by other groups to treat COVID-19 patients experiencing acute respiratory distress with drugs that block IL-6 were disappointing, though more recent studies show promise in combining these medications with the steroid dexamethasone.

Hacohen, who is a professor of medicine at HMS and director of the Broad’s Cell Circuits Program:

“You can ask which of the many thousands of proteins that are circulating in your blood are associated with the actual outcome,” he said, “and whether there is a set of proteins that tell us something.”

Goldberg, who is a professor of emergency medicine at HMS:

They are highly likely to be useful in figuring out some of the underlying mechanisms that lead to severe disease and death in COVID-19,” she said, noting her gratitude to the patients involved in the study. Their samples are already being used to study other aspects of COVID-19, such as identifying the qualities of antibodies that patients form against the virus.

SOURCES

Original Research

Filbin MR, Mehta A, et al. Longitudinal proteomic analysis of plasma from patients with severe COVID-19 reveal patient survival-associated signatures, tissue-specific cell death, and cell-cell interactionsCell Reports Medicine. Online April 30, 2021. DOI: 10.1016/j.xcrm.2021.100287.

Adapted from a press release originally issued by Massachusetts General Hospital.

https://www.broadinstitute.org/news/researchers-identify-protein-%E2%80%9Csignature%E2%80%9D-severe-covid-19

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00115-4

Read Full Post »

COVID-related financial losses at Mass General Brigham

Reporter: Aviva Lev-Ari, PhD, RN

Based on

Mass General Brigham reports COVID-related financial losses not as bad as expected

By Priyanka Dayal McCluskey Globe Staff,Updated December 11, 2020, 3:02 p.m.

START QUOTE

The state’s largest hospital system on Friday reported the worst financial loss in its history while fighting the COVID-19 pandemic — but still ended the fiscal year in better shape than expected.

Mass General Brigham, formerly known as Partners HealthCare, lost $351 million on operations in the fiscal year that ended Sept. 30. In 2019, the system recorded a gain of $382 million.

The loss, however, is not as great as projected, thanks in part to an infusion of federal aid and patients returning to hospitals in large numbers after the first COVID surge receded.

“2020 is like no other year,” said Peter Markell, chief financial officer at Mass General Brigham, which includes Massachusetts General Hospital, Brigham and Women’s Hospital, and several community hospitals. “At the end of the day, we came out of this better than we thought we might.”

Total revenue for the year remained relatively stable at about $14 billion.

When the pandemic first hit Massachusetts in March, hospitals across the state suddenly experienced sharp drops in revenue because they canceled so much non-COVID care to respond to the crisis at hand. They also faced new costs related to COVID, including the personal protective equipment needed to keep health care workers safe from infection.

Federal aid helped to make up much of the losses, including $546 million in grant money that went to Mass General Brigham. The nonprofit health system also slashed capital expenses in half, by about $550 million, and temporarily froze employee wages and cut their retirement benefits.

Among the unusual new costs for Mass General Brigham this year was the expense of building a field hospital, Boston Hope, at the Boston Convention and Exhibition Center. The project cost $15 million to $20 million, Markell said, and Mass General Brigham is working to recoup those costs from government agencies.

The second surge of COVID, now underway, could hit hospitals’ bottom lines again, though Markell expects a smaller impact this time. One reason is because hospitals are trying to treat most of the patients who need care for conditions other than COVID even while treating growing numbers of COVID patients. In the spring, hospitals canceled vastly more appointments and procedures in anticipation of the first wave of COVID.

Mass General Brigham hospitals were treating more than 300 COVID patients on Friday, among the more than 1,600 hospitalized across the state.

Steve Walsh, president of the Massachusetts Health & Hospital Association, said hospitals across the state will need more federal aid as they continue battling COVID into the new year.

“The financial toll of COVID-19 has been felt by every hospital and health care organization in the Commonwealth,” he said. “Those challenges will continue during 2021.”


Priyanka Dayal McCluskey can be reached at priyanka.mccluskey@globe.com. Follow her on Twitter @priyanka_dayal.

END QUOTE

SOURCE

https://www.bostonglobe.com/2020/12/11/business/mass-general-brigham-reports-covid-related-financial-losses-better-than-expected/?p1=Article_Inline_Related_Box

Integration of Mass General Hospital and Brigham Women’s Hospital was accelerated by the COVID-19 pandemic

Reporter: Aviva Lev-Ari, PhD, RN

BASED on

At Mass General Brigham, a sweeping effort to unify hospitals and shed old rivalries

Executives say greater cooperation is necessary to stay relevant in a dynamic and competitive health care industry. But the aggressive push to integrate is stirring tensions and sowing discontent among doctors and hospital leaders.

By Priyanka Dayal McCluskey and Larry Edelman Globe Staff and Globe Columnist,Updated March 27, 2021, 6:15 p.m.125

https://www.bostonglobe.com/2021/03/27/business/mass-general-brigham-sweeping-effort-unify-hospitals-shed-old-rivalries/?s_campaign=breakingnews:newsletter

START QUOTE

The work of integration was accelerated by the COVID-19 pandemic. As patients flooded hospitals last spring, Mass General Brigham — not each of its individual hospitals — set pandemic policies, from what kind of personal protective equipment health care providers should wear, to which visitors were allowed inside hospitals, to how employees would be paid if they were out sick with the virus.

During the winter surge of COVID, Mass General Brigham officials closely tracked beds across their system and transferred patients daily from one hospital to another to ensure that no one facility became overwhelmed.

And, in the early months of the pandemic, the company dropped the name Partners, which meant little to patients, and unveiled a new brand to reflect the strength of its greatest assets, MGH and the Brigham.

Officials at the nonprofit health system have instructeddepartment heads across their hospitals to coordinate better, so, for example, if a patient needs surgery at the Brigham but is facing a long wait, they can refer that patient to another site within Mass General Brigham.

Some executives want patients, eventually, to be able to go online and book appointments at any Mass General Brigham facility, as easily as they make reservations for dinner or a hotel.

Walls described it like this: “How do we put things together that make things better and easier for patients, and leave alone things that are better where they are?

“We’re not going to push things together that don’t fit together,” he said.

And yet the aggressive pursuit of “systemness,” as executives call it, is taking a toll. Physicians and hospital leaders are struggling with the loss of control over their institutions and worried that the new era of top-down management threatens to homogenize a group of hospitals with different cultures and identities.

Veteran physicians and leaders have been surprised and upset by the power shift that is stripping them of the ability to make key decisions and unhappy with abrupt changes they feel are occurring with little discussion. Most are uncomfortable sharing their concerns publicly.

“If you’re not on the train, you’re getting run over by the train,” said one former Mass General Brigham executive who requested anonymity in orderto speak openly. “It’s not an environment to invite debate.”

Amid the restructuring, senior executives are departing in droves. They include the CEO of the MGH physicians group, Dr. Timothy Ferris; Brigham and Women’s president Dr. Elizabeth Nabel; chief financial officer of the system, Peter Markell; Cooley Dickinson Hospital president Joanne Marqusee; and president of Spaulding Rehabilitation Network, David Storto.

Some also fear the internal discord could hinder Mass General Brigham’s ability to attract talented leaders.

Top executives acknowledge there is angst — “Change is hard,” Klibanski said — but are pushing ahead.

MORE

https://www.bostonglobe.com/2021/03/27/business/mass-general-brigham-sweeping-effort-unify-hospitals-shed-old-rivalries/?s_campaign=breakingnews:newsletter

Read Full Post »

Comparing COVID-19 Vaccine Schedule Combinations, or “Com-COV” – First-of-its-Kind Study will explore the Impact of using eight different Combinations of Doses and Dosing Intervals for Different COVID-19 Vaccines

Reporter: Aviva Lev-Ari, PhD, RN

 

The UK’s COVID-19 vaccine rollout commenced in December, and requires an individual to receive two doses of the same vaccine, either Pfizer/BioNTech’s BNT162b2 or AstraZeneca/Oxford’s ChAdOx1, with a maximum interval of 12 weeks between doses. As of February 3, 10 million first doses have been administered.

Com-COV has been classified as an “Urgent Public Health” study by the National Institutes for Health and Research (NIHR), and it’s hoped that the data produced may offer greater flexibility for vaccine delivery going forward.

“Given the inevitable challenges of immunizing large numbers of the population against COVID-19 and potential global supply constraints, there are definitely advantages to having data that could support a more flexible immunization program, if ever needed and approved by the medicines regulator,” Jonathan Van-Tam, deputy chief medical officer and senior responsible officer for the study, said in a press release.

The study will run for a 13-month period and will recruit over 800 patients across eight sites in the UK, including London – St George’s and UCL, Oxford, Southampton, Birmingham, Bristol, Nottingham and Liverpool.

Com-COV has eight different arms that will test eight different combinations of doses and dose intervals. This is tentative and subject to change should more COVID-19 vaccines be approved for use in the UK. The eight arms include the following dose combinations:

  • Pfizer/BioNTech and Pfizer/BioNTech – 28 days apart
  • Pfizer/BioNTech and Pfizer/BioNTech – 12 weeks apart – (control group)
  • Oxford/AstraZeneca and Oxford/AstraZeneca – 28 days apart
  • Oxford/AstraZeneca and Oxford/AstraZeneca – 12 weeks apart – (control group)
  • Oxford/AstraZeneca and Pfizer/BioNTech – 28 days apart
  • Oxford/AstraZeneca and Pfizer/BioNTech – 12 weeks apart
  • Pfizer/BioNTech and Oxford/AstraZeneca – 28 days apart
  • Pfizer/BioNTech and Oxford/AstraZeneca – 12 weeks apart

Aside from the logistical benefits of using alternative vaccines, there is scientific value to exploring how different vaccines and doses affect the human immune system.

Dr Peter English, consultant in communicable disease control, pointed out that the antigen used across the currently authorized COVID-19 vaccines is the same Spike protein. Therefore, the immune system can be expected to respond just as well if a different product is used for boosting. “It is also the case that many vaccines work better if a different vaccine is used for boosting – an approach described as heterologous boosting,” English said, referencing previously successful trials using Hepatitis B vaccines.

“It is also even possible that by combining vaccines, the immune response could be enhanced giving even higher antibody levels that last longer; unless this is evaluated in a clinical trial we just won’t know,” added Van-Tam.

If warranted by the study data, the Medicines and Healthcare products Regulatory Agency may consider reviewing and authorizing modifications to the UK’s vaccine regimen approach – but only time will tell.

“We need people from all backgrounds to take part in this trial, so that we can ensure we have vaccine options suitable for all. Signing up to volunteer for vaccine studies is quick and easy via the NHS Vaccine Research Registry,” Professor Andrew Ustianowski, national clinical lead for the NIHR COVID Vaccine Research Program, said

SOURCE

First-of-its-Kind Study Will Test Combination of Different COVID-19 Vaccines | Technology Networks

https://www.technologynetworks.com/biopharma/news/first-of-its-kind-study-will-test-combination-of-different-covid-19-vaccines-345245?utm_campaign=NEWSLETTER_TN_Biopharma

WATCH VIDEO

Different Types of COVID-19 Vaccines With Dr Seth Lederman Video | Technology Networks

https://www.technologynetworks.com/biopharma/videos/different-types-of-covid-19-vaccines-with-dr-seth-lederman-345207

Read Full Post »

Allocation and Prioritization of Vaccine Dose Administration Schedules: Cover more people or Adhere to Immunization Protocol

Curators:

This curation has four parts:

Part 1:

Waiting on the Covid booster would allow more people to be vaccinated sooner.

  • By Michael Segal, MD, PhD

Part 2:

Expert Opinion by Clinical Authority in Practice of Cardiac Imaging:

  • The Voice of Dr. Justin D. Pearlman, MD, PhD, FACC

Part 3:

Expert Opinion by Scientific Authority in Population Biology

  • The Voice of Prof. Marcus W. Feldman, PhD

Part 4:

Summary

  • The Voices of Prof. Stephen J. Williams, PhD and Aviva Lev-Ari, PhD, RN

Introduction

Aviva Lev-Ari
@AVIVA1950

We agree the protocol should not be changed

Quote Tweet

Pearl Freier
@PearlF
FDA’s Peter Marks explained why the 2 dose regimen for Pfizer/BioNtech vaccine shouldn’t be changed to 1 dose in attempt to reach more patients while there’s limited supply. Aside from 95% effectiveness w/ 2 dose regimen based on clinical data, he said no one knows how long 1/n

Pearl Freier
@PearlF

Replying to

1 dose would be effective for & no one knows if only given 1 dose if patient would get an immune response that “would just dwindle” “And we know that can happen because we know already that people who get very mild covid-19 tend to lose their immune responses pretty quickly.” 2/n

Pearl Freier
@PearlF

We need to make sure that those who get the vaccine regimen are people who know they’ve gotten that protection [95% effective]. Because that’s something we know, whereas the other [1 dose] is conjecture. And I would hate for people to change their behavior on the basis of 3/n

Pearl Freier
@PearlF

one dose of vaccine where we don’t know what’s really happening.” Peter Marks/FDA said (6 min mark) youtube.com/watch?v=uePet5 (
Research!America Alliance Member Meeting with Dr. Peter Marks
With several COVID-19 vaccine candidates under FDA review, Dr. Peter Marks, Director of FDA’s Center for Biologics Evaluation and Research (CBER), joined us …
youtube.com

 (she/her/hers)

@lisabari

Replying to

It will be really interesting to learn more about the immune response from J&J’s one dose regimen.

Pearl Freier
@PearlF

I think they’re expecting data from J&J in January

Part 1:

Waiting on the Covid booster would allow more people to be vaccinated sooner.

By Michael Segal, MD, PhD

https://www.wsj.com/articles/a-shot-instead-of-two-at-saving-lives-11607643152

A Shot (Instead of Two) at Saving Lives

Waiting on the Covid booster would allow more people to be vaccinated sooner.

By Michael Segal

Dec. 10, 2020 6:32 pm ET

Recent days brought good news and bad news about coronavirus vaccines. The developments could add up to months of delay in getting most Americans inoculated. But there’s a way to make use of the good news to speed up herd immunity.

The bad news is that in July the U.S. passed up an opportunity to secure by June 2021 more than 100 million doses of the Pfizer vaccine, now expected to receive emergency-use authorization in the next few days. Instead, officials followed a balanced-portfolio strategy that reserved as many as 300 million doses of the AstraZeneca vaccine, whose prospects are unclear.

The good news is that the Pfizer and Moderna vaccines performed at the upper end of expectations, with 95% efficacy after two doses. And intriguingly, Pfizer’s submission to the Food and Drug Administration shows that the efficacy of the vaccine in preventing disease had largely kicked in by two weeks after the first dose, and there was no dramatic increase in efficacy after the booster was given three weeks later.

The protocol in Pfizer’s clinical trial was to give all participants two doses. The FDA is likely to approve this protocol, and standard procedure is to prescribe a drug according to protocol. But we are in a pandemic and supplies of vaccine are inadequate. There’s an alternative: vaccinating as many people as possible with a first dose and waiting on the booster until supplies are plentiful.

The Pfizer study wasn’t designed to put a number on first-dose efficacy, but the data in Pfizer’s “cumulative incidence curves” suggest at least 75% efficacy for two weeks after one dose. The question is whether to use the 100 million doses on 50 million people, of whom two doses would protect roughly 47.5 million, or to give one dose each to 100 million people and protect at least 75 million.

States have the authority to allocate vaccines as they choose, but they’re unlikely to deviate from the study protocol unless a federal authority—whether the Centers for Disease Control and Prevention or a coronavirus “czar”—suggests this as an option.

Even under such an approach, some essential personnel—such as doctors and nurses who work directly with coronavirus patients and health aides who work in multiple nursing homes—should get two doses as soon as possible, given their high-risk role in the pandemic response.

The U.S. will have more than these 100 million doses of the Pfizer vaccine. Some will come from Moderna, and the federal government could use the Defense Production Act to snatch some Pfizer doses that the company contracted to sell to other countries. Even so, supply will be constrained at first, and officials need to think clearly and flexibly about how to allocate the limited doses that will be available soon.

Harvard epidemiologist Michael Mina expressed his disappointment with society’s decision making during the pandemic: “I’m just astounded by the dysfunction, the willingness to just stay the course as hundreds of thousands of people die, and the unwillingness to innovate in literally any way.” Here’s a simple innovation that could save many lives.

Dr. Segal is a neurologist and neuroscientist.

Copyright ©2020 Dow Jones & Company, Inc. All Rights Reserved. 87990cbe856818d5eddac44c7b1cdeb8

Appeared in the December 11, 2020, print edition.

Part 2:

Expert Opinion by Clinical Authority in Practice of Cardiac Imaging:

The Voice of Dr. Justin D. Pearlman, MD, PhD, FACC

From: Justin MDMEPhD <jdpmdphd@gmail.com>

Date: Saturday, December 12, 2020 at 10:40 PM

To: “Aviva Lev-Ari, PhD, RN” <AvivaLev-Ari@alum.berkeley.edu>

Subject: Re: I NEED YOUR EXPERT OPINION on Mickey Segal’s WSJ op-ed on vaccine dose allocation

Michael Segal proposes off-label use of the Pfizer 2-injection Covid-19 vaccine, based on data that suggested “75% protection at 2 weeks.” There was no controlled study reported of any sustained benefit from the single injection beyond 2 weeks, because those who received a first injection of vaccine received the designed booster at 2 weeks. Dr. Segal suggests it would be irresponsible to use the medication in the manner designed and tested. Instead, he could have proposed a study to determine the duration and degree of benefit from a single dose injection. However, one might argue that could delay the release of an effective regimen for the possibility that his proposed 1 dose regimen might be adequate for some, and possibly for more than the two weeks observed. Even if his guess is correct on both counts, both in his guess that the partial benefit at two weeks might be adequate and that it might last longer than the observed two weeks, it could still be deemed irresponsible to impose his guess for obvious reasons. His guess might be wrong, and could deprive many of the regimen that was validated as effective. Diverting an effective validated regimen to a guess could put many in harms way who would have been protected by the designed 2 dose regimen. He admits to low confidence in his recommendation when he proposes that essential workers should get the validated 2-dose regimen. Why does his recommendation stop there – why not propose a quarter dose to 4 times as many, or 1/8 dose to 8 times as many? Why apply the argument just to the two-dose regimen? He could also guess that a half dose of the single injection successful vaccines might be adequate. The motivation to second guess supply choices and doses is understandable, but it is not sound, as it is just a guess, not a validated regimen.

In addition, he also argues for 20-20 hindsight in the government distributing funds to mulitiple vaccines, instead of disproportionate purchase from Pfizer. Trials are limited in size, and further data will be collected on those vaccinated. Balanced investment may save more lives, not fewer, depending on those outcomes.

On Sat, Dec 12, 2020, 8:20 PM Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu> wrote:

Dear Dr. Pearlman,

Please send me 1/2 –1 page as a Critic of 

  • Mickey Segal’s WSJ op-ed on vaccine dose allocation, below

Part 3:

Expert Opinion by Scientific Authority in Population Biology

The Voice of Prof. Marcus W. Feldman, PhD

From: Marcus W Feldman <mfeldman@stanford.edu>

Date: Sunday, December 13, 2020 at 6:52 PM

To: “Aviva Lev-Ari, PhD, RN” <AvivaLev-Ari@alum.berkeley.edu>

Subject: Re: Mickey Segal’s WSJ op-ed on vaccine dose allocation

RE Segal’s note:

We need more details on the longer term efficacy of the one-dose regimen. Once we have such data, the question of whether 100 million one-dose treatments will be more protective of the population than 50 million two-dose treatments can be addressed. The question of how many hospitalizations and/or deaths would be avoided by going straight to the one-dose regimen can’t be answered. Both approaches leave unanswered whether the transmission of the virus from a vaccinated person is reduced. I would estimate that we need 300 million 2-dose treatments to vaccinate all under 16 year olds.

On Dec 13, 2020, at 1:56 PM, Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu> wrote:

Dear Prof. Feldman,

Please send me 1/2 –1 page as a Critic of 

  • Mickey Segal’s WSJ op-ed on vaccine dose allocation, below

Part 4:

Summary

The Voices of Prof. Stephen J. Williams, PhD and Aviva Lev-Ari, PhD, RN

The Voice of Prof. Stephen J. Williams, PhD

In light of just approved Moderna vaccine, AstraZenaca & JNJ forthcoming vaccine and the approved Pfizer BioNTech coverage should be over 200 million in US, making rationing of second booster shot unnecessary.  However, there is still a concern among the developing and underdeveloped nations that access to these vaccines will be restricted.

The following curation are articles related to this matter from the AAAS and CDC.

CDC advisory panel takes first shot at prioritizing who gets the first shots of COVID-19 vaccines
By Jon CohenDec. 1, 2020 , 8:25 PM
Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

Health care workers and elderly people living in long-term care facilities should receive top priority for COVID-19 vaccines in the United States if, as expected, one or more becomes available next month in limited supply. That’s what a group that advises the U.S. Centers for Disease Control and Prevention (CDC) on such fraught issues decided today in a near-unanimous vote.

After hearing detailed presentations from CDC scientists who explained the rationale for this specific prioritization scheme, the Advisory Committee on Immunization Practices (ACIP) voted 13 to one to support their proposal. Under the scheme, the first phase of vaccination, known as 1a, would begin with about 21 million health care workers and about 3 million adults who live in long-term care facilities. As spelled out in the 4-hour-long virtual meeting, these groups are at highest risk of becoming seriously ill or dying from COVID-19, and protecting them first, in turn, reduces the burden on society.

“I agree strongly with the decision of the committee,” says Stanley Perlman, a veteran coronavirus researcher and clinician at the University of Iowa who advised ACIP but is not part of it. “The discussions were incredibly thoughtful with everyone recognizing that we needed to make difficult choices. Of course, these allocation issues will become irrelevant once there are enough doses of useful vaccines.”

‘Just beautiful’: Another COVID-19 vaccine, from newcomer Moderna, succeeds in large-scale trial
By Jon CohenNov. 16, 2020 , 7:00 AM
Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

SIGN UP FOR OUR DAILY NEWSLETTER
Get more great content like this delivered right to you!

Now, there are two. Another COVID-19 vaccine using the same previously unproven technology as the vaccine from Pfizer and BioNTech, the U.S. and German companies that reported success on 9 November, appears to work remarkably well. And this time, the maker, U.S. biotech Moderna, is releasing a bit more data to back its claim than the other two companies.

An independent board monitoring Moderna’s 30,000-person vaccine trial met on Sunday and reported to the company and U.S. government health officials that only five people in the vaccinated group developed confirmed cases of COVID-19, whereas 90 people who received placebo shots became ill with the disease. That’s an efficacy of 94.5%, the company reported in a press release this morning. Although the clinical trial measurement may not translate into an equally high level of real-world protection, the success indicates the vaccine is Iikely more than effective enough to stop the pandemic if it can be widely distributed.

“That efficacy is just beautiful, and there’s no question about the veracity of it either,” says Lawrence Corey, a virologist at the Fred Hutchinson Cancer Research Center who co-led the clinical trials network that is testing the vaccine.

Moderna’s COVID-19 vaccine ready to ship pending FDA approval -U.S. health chief

Source: https://www.reuters.com/article/health-coronavirus-usa-azar-idUSKBN28R265?taid=5fdc062c54859c0001437b9b&utm_campaign=trueanthem&utm_medium=trueanthem&utm_source=twitter

WASHINGTON (Reuters) – U.S. Health and Human Services Secretary Alex Azar on Thursday said nearly 6 million doses of Moderna Inc’s experimental COVID-19 vaccine were poised to ship nationwide as soon as it secures Food and Drug Administration approval. Azar, in an interview on CNBC, said federal health officials had allotted 5.9 million doses to send to the nation’s governors, who are managing each state’s distribution. “We’re ready to start shipping this weekend to them for rollout Monday, Tuesday, Wednesday of next week. We’re ready to go,” he said. An FDA panel of outside advisers is weighing the safety and effectiveness of Moderna’s vaccine candidate at a meeting on Thursday. The agency will weigh the committee’s conclusions in making its approval decision.

The strategy seems to have been produce multiple vaccines from multiple sources which reduce the strain on manufacturing of required doses.
However, many underdeveloped nations as well as developing nations are worried about the nationalism of access to these vaccines.  Please read below:

Abstract

The 2030 Agenda for Sustainable Development (AfSD) has the vision to leave no one behind, particularly low-income countries. Yet COVID-19 seems to have brought up new rules and approaches. Through document and critical discourse analysis, it emerges that there has been a surge in COVID-19 vaccines and treatments nationalism. Global solidarity is threatened, with the USA, United Kingdom, European Union and Japan having secured 1.3 billion doses of potential vaccines as of August 2020. Vaccines ran out even before their approval with three candidates from Pfizer-BioNTech, Moderna and AstraZeneca having shown good Phase III results in November 2020. Rich countries have gone years ahead in advance vaccines and treatments purchases. This is a testimony that the 2030 AfSD, especially SDG 3 focusing on health will be difficult to achieve. Low-income countries are left gasping for survival as the COVID-19 pandemic relegates them further into extreme poverty and deeper inequality. The paper recommends the continued mobilisation by the World Health Organisation and other key stakeholders in supporting the GAVI vaccine alliance and the Coalition for Epidemic Preparedness Innovations (COVAX) global vaccines initiative that seeks to make two billion vaccine doses available to 92 low and middle-income countries by December 2021.

Others have voiced their concerns on this matter:

 

Reserving coronavirus disease 2019 vaccines for global access: cross sectional analysis

From: Anthony D So 1 2Joshua Woo 2 BMJ2020 Dec 15;371:m4750. doi: 10.1136/bmj.m4750.

Abstract

Objective: To analyze the premarket purchase commitments for coronavirus disease 2019 (covid-19) vaccines from leading manufacturers to recipient countries.

Design: Cross sectional analysis.

Data sources: World Health Organization’s draft landscape of covid-19 candidate vaccines, along with company disclosures to the US Securities and Exchange Commission, company and foundation press releases, government press releases, and media reports.

Eligibility criteria and data analysis: Premarket purchase commitments for covid-19 vaccines, publicly announced by 15 November 2020.

Main outcome measures: Premarket purchase commitments for covid-19 vaccine candidates and price per course, vaccine platform, and stage of research and development, as well as procurement agent and recipient country.

Results: As of 15 November 2020, several countries have made premarket purchase commitments totaling 7.48 billion doses, or 3.76 billion courses, of covid-19 vaccines from 13 vaccine manufacturers. Just over half (51%) of these doses will go to high income countries, which represent 14% of the world’s population. The US has reserved 800 million doses but accounts for a fifth of all covid-19 cases globally (11.02 million cases), whereas Japan, Australia, and Canada have collectively reserved more than one billion doses but do not account for even 1% of current global covid-19 cases globally (0.45 million cases). If these vaccine candidates were all successfully scaled, the total projected manufacturing capacity would be 5.96 billion courses by the end of 2021. Up to 40% (or 2.34 billion) of vaccine courses from these manufacturers might potentially remain for low and middle income countries-less if high income countries exercise scale-up options and more if high income countries share what they have procured. Prices for these vaccines vary by more than 10-fold, from $6.00 (£4.50; €4.90) per course to as high as $74 per course. With broad country participation apart from the US and Russia, the COVAX Facility-the vaccines pillar of the World Health Organization’s Access to COVID-19 Tools (ACT) Accelerator-has secured at least 500 million doses, or 250 million courses, and financing for half of the targeted two billion doses by the end of 2021 in efforts to support globally coordinated access to covid-19 vaccines.

Conclusions: This study provides an overview of how high income countries have secured future supplies of covid-19 vaccines but that access for the rest of the world is uncertain. Governments and manufacturers might provide much needed assurances for equitable allocation of covid-19 vaccines through greater transparency and accountability over these arrangements.

The Voice of Adina Hazan, PhD

I have a few issues with the proposal and the asserted outcomes:

The author suggests that back in July 2020 “the U.S. passed up an opportunity to secure by June 2021 more than 100 million doses of the Pfizer vaccine…[by] follow[ing] a balanced-portfolio strategy”. By stating that the U.S. “passed up an opportunity” at that time when all available evidence could not indicate which vaccine would prove successful is taking a “hindsight is 2020” approach. Instead, an all-or-nothing portfolio in July 2020 for one vaccine over another would have been at best unwise and at worst could have passed up the “right” vaccine.

In addition, the author’s core suggestion is that every person in America and the world needs the vaccine at the same time, aka as soon as possible. Considering the incredibly striated outcomes of patients that contract COVID-19, this is not the case. We know that males up until 85 years old with have a much worse prognosis than women, for example1. In addition, all data suggests that the lowest risk group is children, with a death rate in the U.S. of 0.1%1. Trying to vaccinate all children with a vaccine whose long-term effects are, at this time, unknown, for a disease with such a low death rate is not urgent and may warrant waiting for more evidence. Instead of trying to inoculate everyone as fast as possible, the two-dose approach that is currently implemented ensures that those most at risk receive the maximum protection, instead of leaving them at higher risks even after vaccination. In this way, the vaccine will do what it was originally intended to do: protect the most vulnerable immediately, and in turn begin to alleviate the strain on the overall population as a result of this disease.

  1. S. CDC website (Deaths by Age Group, 12/18/2020)

The Voice of Aviva Lev-Ari, PhD, RN

  • I recommand to adhere to administration protocol.
  • I agree with Dr. Joel Jertock:

It is very clear that the current COVID vaccination protocols call for two shots, three weeks apart, for maximum protection.

Limiting personnel to a single shot, “to spread the available vaccines further” just means wasting those doses.  It is similar to taking an antibiotic for only 5 days instead of the recommended 10 days, “to make the pills last longer.”

References on Vaccine Development 

Development of Medical Counter-measures for 2019-nCoV, CoVid19, Coronavirus

Read Full Post »

12/5/2020

Regeneron’s Covid Antibody coktail has been cleared for emergency use by the FDA. The emergency authorization for REGN-COV2, a combination of monoclonal antibodies casiriviamb and imdevimab, marks the second for the antibody therapy. The first emergency authorization was given to Eli Lily’s bamlanivimab.

The difference that REGN-COV2 is a concoction of several drugs, whereas Lilly’s treatment contains only one drug, the two emergency authorizations  are almost identical. They treat both for mild-to-moderate COVID-19 patients at least 12 years of age who are not hospitalized but are at high risk for progressing to severe COVID-19.

SOURCE

https://www.fiercepharma.com/pharma/regeneron-following-lilly-s-footsteps-wins-fda-emergency-nod-for-covid-19-antibody-cocktail


Regeneron’s new antibody cocktail drug, REGN-COV2

Reporter : Irina Robu, PhD

Regeneron,  leading biotechnology company using the power of science to bring new medicines to patients in need answered quickly to the COVID-19 pandemic and found an antibody cocktail  as the pandemic numbers increase in the U.S. The antibody cocktail, also known as REGN-COV2 antibody combination therapy is an investigational medicine, and its safety and efficacy have not been fully evaluated by any regulatory authority.

REGN-COV2 is being studied in four ongoing late-stage clinical trials: two Phase 2/3 trials for the treatment of hospitalized and non-hospitalized COVID-19 patients, Phase 3 RECOVERY trial of hospitalized COVID-19 patients in the UK, and a Phase 3 trial for the prevention of COVID-19 in uninfected people who are at high-risk of exposure to a COVID-19 patient. The Phase 3 prevention trial is being jointly conducted with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

The company expects approval from FDA on its antibody cocktail and expect to have 2.4-gram doses ready for about 80,000 patients at the end of November and 200,000 doses at the beginning of January.  At the same time, Regeneron partnered with Roche to expand its capacity further by increasing its manufacturing capacity.

Regeneron come in COVID-19 research early this year as the outbreak was in its early stages, testing hundreds of virus-neutralizing antibodies in mice and seeing how they compared with antibodies from human survivors of the novel coronavirus.

SOURCE

https://www.fiercepharma.com/manufacturing/regeneron-predicts-300-000-covid-19-cocktail-doses-ready-by-january-and-substantially

 

Read Full Post »

Detecting SARS-COV-2 antibodies in serum and plasma samples

Reporter: Irina Robu, PhD

Convalescent plasma therapy is a possible treatment under investigation where antibodies from recovered patients are transfused to current COVID-19 patients with the intent to help them fight the infection and buy time until their immune system can produce antibodies. Yet, not all recovered patients have the same quantity of antibody titers suitable for such transfusions. In some patients it will minimize the severity of the disease length.

The U.S. Food and Drug Administration authorized convalescent plasma therapy for patients with coronavirus disease 2019 and it permitted to be used during the pandemic because there is no approved treatment for COVID-19. The donated blood is processed to remove cells, leaving behind liquid and antibody.   

Companies like Forte Bío are developing instruments such as Octet HTX Instrument, Octet RED384 Octet RED96e Instrument and Octet K2 Instrument to detect SARS-COV-2 antibodies in serum and plasma samples. The Octet technology allows quantification with high resolution comparable to an HPLC . The instrument utilizes BLI enabling label-free detection for protein quantitation and kinetic characterization at unmatched speed and throughput. The instrument can  measure up to 96 samples simultaneously allowing both unlimited characterization capacity for various applications and custom assay tailoring to maximize analytical throughput or sensitivity and preventing bottlenecks. 

 How are antibodies tested ?

  1. Immobilize a virus protein such as the receptor binding domain (RBD) of the SARS CoV-2 spike protein.
  2. Dip the coronavirus biosensor into diluted patient plasma or serum samples.
  3. Block the biosensor with non-relevant serum or blocking buffer if needed to prevent non-specific binding.

Even the researchers believe that the risk to donors is low, there are additional risks such as allergic reactions, lung damage, difficulty breathing or infections such as HIV, hepatitis B and Donated blood must be tested for safety prior to administering to patients.

What to expect ? It is up to the doctor treating the patient, if convalescent plasma therapy is an option.  Even though data from clinical trials suggest that convalescent plasma may diminish the severity or duration of the COVID19, more research is needed to determine if convalescent plasma therapy is an effective treatment.

SOURCE

https://www.fortebio.com/covid19research19research

https://www.medrxiv.org/content/10.1101/2020.07.17.20156281v1

 

Other related articles were published in this Open Access Online Scientific Journal including the following:

https://pharmaceuticalintelligence.com/2020/05/18/race-to-develop-antibody-drugs-for-covid-19

https://pharmaceuticalintelligence.com/2020/05/18/race-to-develop-antibody-drugs-for-covid-19

 

 

Read Full Post »

FDA Authorizes Convalescent Plasma for COVID-19 Patients

Reporter: Irina Robu, PhD

The U.S. Food and Drug Administration authorized convalescent plasma therapy in August 2020 for people with coronavirus disease 2019. The convalescent plasma shows promising efficacy in hospitalized patients with COVID-19 and the benefits outweighs the risk  and FDA gave emergency use authorization. The approval is not  for any particular convalescent plasma product, but for preparation collected by FDA registered blood establishments from individuals whose plasma contains anti-SARS-CoV-2 antibodies, and who meet all donor eligibility requirements.

What exactly is convalescent plasma ? It is blood donated from patients who have recovered from COVID-19 has antibodies to the virus that causes it. The donated blood is processed by removing blood cells, leaving behind plasma and antibodies, which can be given to people with COVID-19 to boost their ability to fight the virus. According to FDA, COVID-19 covalescent plasma with high antibody titer can be effective in reducing mortality in hospitalized patients, but low antibody titer can be used based on health care provider discretion.  FDA also indicated that COVID-19 convalescent plasma may be effective in lessening the severity or shortening the length of COVID-19 illness in some hospitalized patients.

To confirm the results, the FDA recommended randomized trialsas COVID-19 convalescent plasma does not yet describe a new standard of care based on the current available evidence.

SOURCE

https://www.medpagetoday.com/infectiousdisease/covid19/88225?xid=NL_breakingnewsalert_2020-08-23

Read Full Post »

The Impact of COVID-19 on the Human Heart

Reporters: Justin D. Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

The Voice of Dr. Pearlman:

 

 

Editorial

September 22/29, 2020

The COVID-19 Pandemic and the JAMA Network

In 13 Viewpoints in this issue,214 JAMA Network editors reflect on the clinical, public health, operational, and workforce issues related to COVID-19 in each of their specialties. Questions and concerns they identify in their clinical communities include the following:

  • Benefits and harms of treatments and identifying mortality risk markers beyond age and comorbidities

  • Cardiovascular consequences of COVID-19 infection, including risks to those with comorbid hypertension and risks for myocardial injury

  • Risk for direct central nervous system invasion and COVID-19 encephalitis and for long-term neuropsychiatric manifestations in a post–COVID-19 syndrome

  • Risks related to SARS-CoV-2 infection for patients with compromised immunity, such as those receiving treatment for cancer

  • Challenges unique to patients with acute kidney injury and chronic kidney disease

  • Risks of viral transmission from aerosol-generating procedures, including most minimally invasive surgeries, and the need for eye protection as well as personal protective equipment as part of universal precautions

  • The prevalence and pathophysiology of skin findings in patients with COVID-19, determining if they are primary or secondary cutaneous manifestations of infection, and how best to manage them

  • The prevalence and significance of eye findings in patients with COVID-19 and the risk of transmission and infection through ocular surfaces

  • The role of anticoagulation for managing the endotheliopathy and coagulopathy characteristic of the infection in some patients

  • Developmental effects on children of the loss of family routines, finances, older loved ones, school and education, and social-based activities and milestone events

  • Effects of the pandemic, mitigation efforts, and economic downturn on the mental health of patients and frontline clinicians

  • Seasonality of transmission as the pandemic enters its third season

  • How to implement reliable seroprevalence surveys to document progression of the pandemic and effects of public health measures

  • Effects of the pandemic on access to care and the rise of telehealth

  • Consequences of COVID-19 for clinical capabilities, such as workforce availability in several specialties, delays in performing procedures and operations, and implications for medical education and resident recruitment.

Additional important questions that require careful observation and research include

  • Randomized evaluations of treatment: what is effective and safe, and what timing of which drug will reduce morbidity and mortality? Will a combination of therapies be more effective than any single drug?
  • Randomized evaluations of preventive interventions, including convalescent plasma, monoclonal antibodies, and vaccines. Which are effective and safe enough to prevent COVID-19 at a population level?
  • How can COVID-19 vaccines and therapeutics be distributed and paid for in ways that are fair and equitable?
  • Is immunity complete or partial, permanent or temporary, what is its mechanism, and how best is it measured? Can the virus mutate around host defenses?
  • How important are preadolescent children to the spread of infection to older family members and adult communities, and what are the implications for parent, caregiver, and teacher personal risk and disease transmission?
  • Is SARS-CoV-2 like influenza (continually circulating without or with seasonality), measles (transmissible but containable beneath threshold limits), or smallpox and polio (eradicable, or nearly so)?
  • Has the pandemic fundamentally altered the way health care is financed and delivered? By shining a spotlight on health inequities, can the pandemic motivate changes in health care finance, organization, and delivery to reduce those inequities?
  • Cardiology and COVID-19

Cardiology and COVID-19 – Original Article

Bonow  RO, O’Gara  PT, Yancy  CW.  Cardiology and COVID-19.   JAMA. Published online September 22, 2020. doi:10.1001/jama.2020.15088
Article Google Scholar

The initial reports on the epidemiology of coronavirus disease 2019 (COVID-19) emanating from Wuhan, China, offered an ominous forewarning of the risks of severe complications in elderly patients and those with underlying cardiovascular disease, including the development of acute respiratory distress syndrome, cardiogenic shock, thromboembolic events, and death. These observations have been confirmed subsequently in numerous reports from around the globe, including studies from Europe and the US. The mechanisms responsible for this vulnerability have not been fully elucidated, but there are several possibilities. Some of these adverse consequences could reflect the basic fragility of older individuals with chronic conditions subjected to the stress of severe pneumonia similar to influenza infections. In addition, development of type 2 myocardial infarction related to increased myocardial oxygen demand in the setting of hypoxia may be a predominant concern, and among patients with chronic coronary artery disease, an episode of acute systemic inflammation might also contribute to plaque instability, thus precipitating acute coronary syndromes, as has also been reported during influenza outbreaks.

However, in the brief timeline of the current pandemic, numerous publications highlighting the constellation of observed cardiovascular consequences have emphasized certain distinctions that appear unique to COVID-19.1 Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gains entry via the upper respiratory tract, its affinity and selective binding to the angiotensin-converting enzyme 2 (ACE2) receptor, which is abundant in the endothelium of arteries and veins as well as in the respiratory tract epithelium, create a scenario in which COVID-19 is as much a vascular infection as it is a respiratory infection with the potential for serious vascular-related complications. This may explain why hypertension is one of the cardiovascular conditions associated with adverse outcomes. In the early stages of the pandemic, the involvement of the ACE2 receptor as the target for viral entry into cells created concerns regarding the initiation or continuation of treatment with ACE inhibitors and angiotensin receptor antagonists in patients with hypertension, left ventricular dysfunction, or other cardiac conditions. Subsequently, many studies have shown that these drugs do not increase susceptibility to infection or increase disease severity in those who contract the disease,2 thus supporting recommendations from academic societies that these drugs should not be discontinued in patients who develop COVID-19 infections.

Thrombosis, arterial or venous, is a hallmark of severe COVID-19 infections, related both to vascular injury and the prothrombotic cytokines released during the intense systemic inflammatory and immune responses.3 This sets the stage for serious thrombotic complications including acute coronary syndromes, ischemic strokes, pulmonary embolism, and ischemic damage to multiple other organ systems. Such events can complicate the course of any patient with COVID-19 but would be particularly devasting to individuals with preexisting cardiovascular disease.

Another unique aspect of COVID-19 infections that is not encountered by patients with influenza is myocardial injury, manifested by elevated levels of circulating troponin, creatinine kinase-MB, and myoglobin. Hospitalized patients with severe COVID-19 infections and consequent evidence of myocardial injury have a high risk of in-hospital mortality.4 Troponin elevations are most concerning, and when accompanied by elevations of brain natriuretic peptide, the risk is further accentuated. Although myocardial injury could reflect a COVID-19–related acute coronary event, most patients with troponin elevations who undergo angiography do not have epicardial coronary artery obstruction. Rather, those with myocardial injury have a high incidence of acute respiratory distress syndrome, elevation of D-dimer levels, and markedly elevated inflammatory biomarkers such as C-reactive protein and procalcitonin, suggesting that the combination of hypoxia, microvascular thrombosis, and systemic inflammation contributes to myocardial injury. Myocarditis is a candidate explanation for myocardial injury but has been difficult to confirm consistently. However, features of myocarditis have been reported in case reports5 based on clinical presentation and results of noninvasive imaging, but thus far confirmation of myocarditis based on myocardial biopsy or autopsy examinations has been a rare finding.6 Instead, myocardial tissue samples more typically show vascular or perivascular inflammation (endothelialitis) without leukocytic infiltration or myocyte damage.

There remain important unknowns regarding the intermediate and long-term sequelae of COVID-19 infection among hospital survivors. In an autopsy series of patients who died from confirmed COVID-19 without clinical or histological evidence of fulminant myocarditis,7 viral RNA was identified in myocardial tissue in 24 of 39 cases, with viral load of more than 1000 copies/μg of RNA in 16 cases. A cytokine response panel demonstrated upregulation of 6 proinflammatory genes (tumor necrosis factor, interferon γ, CCL4, and interleukin 6, 8, and 18) in the 16 myocardial samples with the high viral RNA levels.

Whether a subclinical viral load and associated cytokine response such as this in survivors of COVID-19 could translate into subsequent myocardial dysfunction and clinical heart failure require further investigation. However, the results of a recent biomarker and cardiac magnetic resonance (CMR) imaging study provide evidence to support this concern.6 Among 100 patients who were studied by CMR after recovery from confirmed COVID-19 infection, of whom 67 did not require hospitalization during the acute phase, left ventricular volume was greater and ejection fraction was lower than that of a control group. Furthermore, 78 patients had abnormal myocardial tissue characterization by CMR, with elevated T1 and T2 signals and myocardial hyperenhancement consistent with myocardial edema and inflammation, and 71 patients had elevated levels of high-sensitivity troponin T. Three patients with the most severe CMR abnormalities underwent myocardial biopsy, with evidence of active lymphocytic infiltration.6 It is noteworthy that all 100 patients in this series had negative COVID-19 test results at the time of CMR study (median, 71 days; interquartile range [IQR], 64-92 days after acute infection). The results of these relatively small series should be interpreted cautiously until confirmed by larger series with longer follow-up and with confirmed clinical outcomes. But the findings do underscore the uncertainty regarding the long-term cardiovascular consequences of COVID-19 in patients who have ostensibly recovered. Of note, a randomized clinical trial of anticoagulation to reduce the risk of thrombotic complications in the posthospital phase of COVID-19 infection is under development through the National Institutes of Health’s set of ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) initiatives.

In addition, the indirect effects of COVID-19 have become a major concern. Multiple observations during the COVID-19 pandemic confirm a sudden and inexplicable decline in rates of hospital admissions for ST–segment elevation myocardial infarction and other acute coronary syndromes beginning in March and April 2020. This has been a universal experience, with similar findings reported from multiple countries around the world in single-center observations, multicenter registries, and national databases. A concerning increase in out-of-hospital cardiac arrests has also been reported.8 These data suggest that COVID-19 has influenced health care–seeking behavior resulting in fewer presentations of acute coronary syndromes in emergency departments and more out-of-hospital events. Failure to seek appropriate emergency cardiac care could contribute to the observations of increased number of deaths and cardiac arrests, more than the anticipated average during this period8,9 with worse outcomes among those who ultimately do seek care.10 Recent data suggest that admission rates for myocardial infarction may be returning to baseline,10 but outcomes will improve only if patients seek care promptly and hospital systems are not overwhelmed by COVID-19 surges.

Given the ongoing activity of COVID-19, very clear messaging to the public and patients should include the following: heed the warning signs of heart attack, act promptly to initiate emergency medical services, and seek immediate care in hospitals, which have taken every step needed to be safe places. And especially, the messaging should continuously underscore the most important considerations that have been extant since this crisis began—wear a mask and practice physical distancing. In the meantime, the generation of rigorous evidence to inform best practices for diagnosis and management of COVID-19–related cardiovascular disease is a global imperative.

Corresponding Author: Robert O. Bonow, MD, MS, Division of Cardiology, Northwestern University Feinberg School of Medicine, 676 N St Clair St, Ste 600, Chicago, IL 60611 (r-bonow@northwestern.edu)

SOURCE

https://jamanetwork.com/journals/jama/fullarticle/2770858

Read Full Post »

Sex Differences in Immune Responses that underlie COVID-19 Disease Outcomes

Reporter: Aviva Lev-Ari, PhD, RN and Irina Robu, PhD COVID-19 is a non-discriminatory virus, it can infect anyone from young to old, but it seems that older men are twice more susceptible to it and most likely to become severely sick and die in comparison to women of the same age. Researchers from Yale university, published an article suggesting that men, particularly those over the age of 60 may need to depend more on vaccines to protect themselves from infection. According to their research published in Nature in August 2020, known sex differences between men and women pose challenges to the immune system. Women mount faster and stronger immune responses, possibly because their bodies are equipped to fight pathogens that threaten unborn or newborn children. Over time, an immune system in a constant state of high alert can be harmful. The findings underline the necessity for companies developing coronavirus vaccines to analyze their data by sex and may influence decisions about dosing. Dr. Iwasaki’s team from Yale  analyzed immune responses in 17 men and 22 women who were admitted to the hospital soon after they were infected with the coronavirus. The investigators collected blood, nasopharyngeal swabs, saliva, urine and stool from the patients every three to seven days. The researchers also analyzed data from an additional 59 men and women who did not meet those criteria. Over all, the scientists found, the women’s bodies produced more T cells, which can kill and stop the infection from spreading. Men on the other hand presented  a much weaker activation of T cells and that delay was linked to how sick the men became. The older the men, the weaker their T cell responses. Even though the study provided some more information about why men become sicker when diagnosed with coronavirus than women,  it did not offer a clear reason for the differences between men and women. SOURCE https://www.nature.com/articles/s41586-020-2700-3
Article

This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

Sex differences in immune responses that underlie COVID-19 disease outcomes

Abstract

A growing body of evidence indicates sex differences in the clinical outcomes of coronavirus disease 2019 (COVID-19)1–5. However, whether immune responses against SARS-CoV-2 differ between sexes, and whether such differences explain male susceptibility to COVID-19, is currently unknown. In this study, we examined sex differences in
  • viral loads,
  • SARS-CoV-2-specific antibody titers,
  • plasma cytokines, as well as
  • blood cell phenotyping in COVID-19 patients.
By focusing our analysis on patients with moderate disease who had not received immunomodulatory medications, our results revealed that
  • male patients had higher plasma levels of innate immune cytokines such as IL-8 and IL-18 along with more robust induction of non-classical monocytes. In contrast,
  • female patients mounted significantly more robust T cell activation than male patients during SARS-CoV-2 infection, which was sustained in old age.
  • Importantly, we found that a poor T cell response negatively correlated with patients’ age and was associated with worse disease outcome in male patients, but not in female patients.
  • Conversely, higher innate immune cytokines in female patients associated with worse disease progression, but not in male patients.
  • These findings reveal a possible explanation underlying observed sex biases in COVID-19, and provide an important basis for the development of
  • a sex-based approach to the treatment and care of men and women with COVID-19.

Author information

Affiliations

Consortia

Corresponding author

Correspondence to Akiko Iwasaki.

Read Full Post »

Did FDA Reverse Course on Convalescent Plasma Therapy for COVID-19?

Reporter: Stephen J. Williams, PhD

 

Starting with a timeline of recent announcements by the FDA on convalescent plasma therapy

April 16, 2020

FDA STATEMENT

Coronavirus (COVID-19) Update: FDA Encourages Recovered Patients to Donate Plasma for Development of Blood-Related Therapies

 

As part of the all-of-America approach to fighting the COVID-19 pandemic, the U.S. Food and Drug Administration has been working with partners across the U.S. government, academia and industry to expedite the development and availability of critical medical products to treat this novel virus. Today, we are providing an update on one potential treatment called convalescent plasma and encouraging those who have recovered from COVID-19 to donate plasma to help others fight this disease.

Convalescent plasma is an antibody-rich product made from blood donated by people who have recovered from the disease caused by the virus. Prior experience with respiratory viruses and limited data that have emerged from China suggest that convalescent plasma has the potential to lessen the severity or shorten the length of illness caused by COVID-19. It is important that we evaluate this potential therapy in the context of clinical trials, through expanded access, as well as facilitate emergency access for individual patients, as appropriate.

The response to the agency’s recently announced national efforts to facilitate the development of and access to convalescent plasma has been tremendous. More than 1,040 sites and 950 physician investigators nationwide have signed on to participate in the Mayo Clinic-led expanded access protocol. A number of clinical trials are also taking place to evaluate the safety and efficacy of convalescent plasma and the FDA has granted numerous single patient emergency investigational new drug (eIND) applications as well.

Source: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-encourages-recovered-patients-donate-plasma-development-blood

August 23, 2020

 

Recommendations for Investigational COVID-19 Convalescent Plasma

 

  • FDA issues guidelines on clinical trials and obtaining emergency enrollment concerning convalescent plasma

FDA has issued guidance to provide recommendations to health care providers and investigators on the administration and study of investigational convalescent plasma collected from individuals who have recovered from COVID-19 (COVID-19 convalescent plasma) during the public health emergency.

The guidance provides recommendations on the following:

Because COVID-19 convalescent plasma has not yet been approved for use by FDA, it is regulated as an investigational product.  A health care provider must participate in one of the pathways described below.  FDA does not collect COVID-19 convalescent plasma or provide COVID-19 convalescent plasma.  Health care providers or acute care facilities should instead obtain COVID-19 convalescent plasma from an FDA-registered blood establishment.

Excerpts from the guidance document are provided below.

Background

The Food and Drug Administration (FDA or Agency) plays a critical role in protecting the United States (U.S.) from threats including emerging infectious diseases, such as the Coronavirus Disease 2019 (COVID-19) pandemic.  FDA is committed to providing timely guidance to support response efforts to this pandemic.

One investigational treatment being explored for COVID-19 is the use of convalescent plasma collected from individuals who have recovered from COVID-19.  Convalescent plasma that contains antibodies to severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 (the virus that causes COVID-19) is being studied for administration to patients with COVID-19. Use of convalescent plasma has been studied in outbreaks of other respiratory infections, including the 2003 SARS-CoV-1 epidemic, the 2009-2010 H1N1 influenza virus pandemic, and the 2012 MERS-CoV epidemic.

Although promising, convalescent plasma has not yet been shown to be safe and effective as a treatment for COVID-19. Therefore, it is important to study the safety and efficacy of COVID-19 convalescent plasma in clinical trials.

Pathways for Use of Investigational COVID-19 Convalescent Plasma

The following pathways are available for administering or studying the use of COVID-19 convalescent plasma:

  1. Clinical Trials

Investigators wishing to study the use of convalescent plasma in a clinical trial should submit requests to FDA for investigational use under the traditional IND regulatory pathway (21 CFR Part 312). CBER’s Office of Blood Research and Review is committed to engaging with sponsors and reviewing such requests expeditiously. During the COVID-19 pandemic, INDs may be submitted via email to CBERDCC_eMailSub@fda.hhs.gov.

  1. Expanded Access

An IND application for expanded access is an alternative for use of COVID-19 convalescent plasma for patients with serious or immediately life-threatening COVID-19 disease who are not eligible or who are unable to participate in randomized clinical trials (21 CFR 312.305). FDA has worked with multiple federal partners and academia to open an expanded access protocol to facilitate access to COVID-19 convalescent plasma across the nation. Access to this investigational product may be available through participation of acute care facilities in an investigational expanded access protocol under an IND that is already in place.

Currently, the following protocol is in place: National Expanded Access Treatment Protocol

  1. Single Patient Emergency IND

Although participation in clinical trials or an expanded access program are ways for patients to obtain access to convalescent plasma, for various reasons these may not be readily available to all patients in potential need. Therefore, given the public health emergency that the COVID-19 pandemic presents, and while clinical trials are being conducted and a national expanded access protocol is available, FDA also is facilitating access to COVID-19 convalescent plasma for use in patients with serious or immediately life-threatening COVID-19 infections through the process of the patient’s physician requesting a single patient emergency IND (eIND) for the individual patient under 21 CFR 312.310. This process allows the use of an investigational drug for the treatment of an individual patient by a licensed physician upon FDA authorization, if the applicable regulatory criteria are met.  Note, in such case, a licensed physician seeking to administer COVID-19 convalescent plasma to an individual patient must request the eIND (see 21 CFR 312.310(b)).

To Obtain a Single Patient Emergency IND  

The requesting physician may contact FDA by completing Form FDA 3926 (https://www.fda.gov/media/98616/download) and submitting the form by email to CBER_eIND_Covid-19@FDA.HHS.gov.

FACT SHEET FOR PATIENTS AND PARENTS/CAREGIVERS EMERGENCY USE AUTHORIZATION (EUA) OF COVID-19 CONVALESCENT PLASMA FOR TREATMENT OF COVID-19 IN HOSPITALIZED PATIENTS

  • FDA issues fact sheet for patients on donating plasma

August 23, 2020

 

FDA Issues Emergency Use Authorization for Convalescent Plasma as Potential Promising COVID–19 Treatment, Another Achievement in Administration’s Fight Against Pandemic

 

Today, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for investigational convalescent plasma for the treatment of COVID-19 in hospitalized patients as part of the agency’s ongoing efforts to fight COVID-19. Based on scientific evidence available, the FDA concluded, as outlined in its decision memorandum, this product may be effective in treating COVID-19 and that the known and potential benefits of the product outweigh the known and potential risks of the product.

Today’s action follows the FDA’s extensive review of the science and data generated over the past several months stemming from efforts to facilitate emergency access to convalescent plasma for patients as clinical trials to definitively demonstrate safety and efficacy remain ongoing.

The EUA authorizes the distribution of COVID-19 convalescent plasma in the U.S. and its administration by health care providers, as appropriate, to treat suspected or laboratory-confirmed COVID-19 in hospitalized patients with COVID-19.

Alex Azar, Health and Human Services Secretary:
“The FDA’s emergency authorization for convalescent plasma is a milestone achievement in President Trump’s efforts to save lives from COVID-19,” said Secretary Azar. “The Trump Administration recognized the potential of convalescent plasma early on. Months ago, the FDA, BARDA, and private partners began work on making this product available across the country while continuing to evaluate data through clinical trials. Our work on convalescent plasma has delivered broader access to the product than is available in any other country and reached more than 70,000 American patients so far. We are deeply grateful to Americans who have already donated and encourage individuals who have recovered from COVID-19 to consider donating convalescent plasma.”

Stephen M. Hahn, M.D., FDA Commissioner:
“I am committed to releasing safe and potentially helpful treatments for COVID-19 as quickly as possible in order to save lives. We’re encouraged by the early promising data that we’ve seen about convalescent plasma. The data from studies conducted this year shows that plasma from patients who’ve recovered from COVID-19 has the potential to help treat those who are suffering from the effects of getting this terrible virus,” said Dr. Hahn. “At the same time, we will continue to work with researchers to continue randomized clinical trials to study the safety and effectiveness of convalescent plasma in treating patients infected with the novel coronavirus.”

Scientific Evidence on Convalescent Plasma

Based on an evaluation of the EUA criteria and the totality of the available scientific evidence, the FDA’s Center for Biologics Evaluation and Research determined that the statutory criteria for issuing an EUA criteria were met.

The FDA determined that it is reasonable to believe that COVID-19 convalescent plasma may be effective in lessening the severity or shortening the length of COVID-19 illness in some hospitalized patients. The agency also determined that the known and potential benefits of the product, when used to treat COVID-19, outweigh the known and potential risks of the product and that that there are no adequate, approved, and available alternative treatments.

 

August 24, 2020

Donate COVID-19 Plasma

 

  • FDA posts video and blog about how to donate plasms if you had been infected with COVID

 

https://youtu.be/PlX15rWdBbY

 

 

Please go to https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/donate-covid-19-plasma

to read more from FDA

 

 

August 25, 2020

 

CLINICAL MEMORANDUM From: , OBRR/DBCD/CRS To: , OBRR Through: , OBRR/DBCD , OBRR/DBCD , OBRR/DBCD/CRS Re: EUA 26382: Emergency Use Authorization (EUA) Request (original request 8/12/20; amended request 8/23/20) Product: COVID-19 Convalescent Plasma Items reviewed: EUA request Fact Sheet for Health Care Providers Fact Sheet for Recipients Sponsor: Robert Kadlec, M.D. Assistant Secretary for Preparedness and Response (ASPR) Office of Assistant Secretary for Preparedness and Response (ASPR) U.S. Department of Health and Human Services (HHS) EXECUTIVE SUMMARY COVID-19 Convalescent Plasma (CCP), an unapproved biological product, is proposed for use under an Emergency Use Authorization (EUA) under section 564 of the Federal Food, Drug, and Cosmetic Act (the Act),(21 USC 360bbb-3) as a passive immune therapy for the treatment of hospitalized patients with COVID-19, a serious or life-threatening disease. There currently is no adequate, approved, and available alternative to CCP for treating COVID-19. The sponsor has pointed to four lines of evidence to support that CCP may be effective in the treatment of hospitalized patients with COVID-19: 1) History of convalescent plasma for respiratory coronaviruses; 2) Evidence of preclinical safety and efficacy in animal models; 3) Published studies of the safety and efficacy of CCP; and 4) Data on safety and efficacy from the National Expanded Access Treatment Protocol (EAP) sponsored by the Mayo Clinic. Considering the totality of the scientific evidence presented in the EUA, I conclude that current data for the use of CCP in adult hospitalized patients with COVID-19 supports the conclusion that CCP meets the “may be effective” criterion for issuance of an EUA from section 564(c)(2)(A) of the Act. It is reasonable to conclude that the known and potential benefits of CCP outweigh the known and potential risks of CCP for the proposed EUA. Current data suggest the largest clinical benefit is associated with high-titer units of CCP administered early course of the disease.

Source: https://www.fda.gov/media/141480/download

 

And Today August 26, 2020

  • A letter, from Senator Warren, to Commissioner Hahn from Senate Committee asking for documentation for any communication between FDA and White House

August 25, 2020 Dr. Stephen M. Hahn, M.D. Commissioner of Food and Drugs U.S. Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 Dear Commissioner Hahn: We write regarding the U.S. Food and Drug Administration’s (FDA) troubling decision earlier this week to issue an Emergency Use Authorization (EUA) for convalescent plasma as a treatment for coronavirus disease 2019 (COVID-19).1 Reports suggests that the FDA granted the EUA amid intense political pressure from President Trump and other Administration officials, despite limited evidence of convalescent plasma’s effectiveness as a COVID-19 treatment.2 To help us better understand whether the issuance of the blood plasma EUA was motivated by politics, we request copies of any and all communications between FDA and White House officials regarding the blood plasma EUA.

Source: https://www.warren.senate.gov/imo/media/doc/2020.08.25%20Letter%20to%20FDA%20re%20Blood%20Plasma%20EUA.pdf

…….. which may have been a response to this article

FDA chief walks back comments on effectiveness of coronavirus plasma treatment

 

From CNBC: https://www.cnbc.com/2020/08/25/fda-chief-walks-back-comments-on-effectiveness-of-coronavirus-plasma-treatment.html

PUBLISHED TUE, AUG 25 202010:45 AM EDTUPDATED TUE, AUG 25 20204:12 PM EDT

Berkeley Lovelace Jr.@BERKELEYJR

Will Feuer@WILLFOIA

KEY POINTS

  • The authorization will allow health-care providers in the U.S. to use the plasma to treat hospitalized patients with Covid-19.
  • The FDA’s emergency use authorization came a day after President Trump accused the agency of delaying enrollment in clinical trials for vaccines or therapeutics.
  • The criticism from Trump and action from the FDA led some scientists to believe the authorization, which came on the eve of the GOP national convention, was politically motivated.

FDA Commissioner Dr. Stephen Hahn is walking back comments on the benefits of convalescent plasma, saying he could have done a better job of explaining the data on its effectiveness against the coronavirus after authorizing it for emergency use over the weekend.

Commisioners responses over Twitter

https://twitter.com/SteveFDA/status/1298071603675373569?s=20

https://twitter.com/SteveFDA/status/1298071619236245504?s=20

August 26, 2020

In an interview with Bloomberg’s , FDA Commissioner Hahn reiterates that his decision was based on hard evidence and scientific fact, not political pressure.  The whole interview is at the link below:

https://www.bloomberg.com/news/articles/2020-08-25/fda-s-hahn-vows-to-stick-to-the-science-amid-vaccine-pressure?sref=yLCixKPR

Some key points:

  • Dr. Hahn corrected his initial statement about 35% of people would be cured by convalescent plasma. In the interview he stated:

I was trying to do what I do with patients, because patients often understand things in absolute terms versus relative terms. And I should’ve been more careful, there’s no question about it. What I was trying to get to is that if you look at a hundred patients who receive high titre, and a hundred patients who received low titre, the difference between those two particular subset of patients who had these specific criteria was a 35% reduction in mortality. So I frankly did not do a good job of explaining that.

  • FDA colleagues had frank discussion after the statement was made.  He is not asking for other people in HHS to retract their statements, only is concerned that FDA has correct information for physicians and patients
  • Hahn is worried that people will not enroll due to chance they may be given placebo
  • He gave no opinion when asked if FDA should be an independent agency

 

For more articles on COVID19 please go to our Coronavirus Portal at

https://pharmaceuticalintelligence.com/coronavirus-portal/

 

Read Full Post »

Older Posts »