India's Bharat Biotech scouts international COVID-19 vaccine partners

 

Indian vaccine maker Bharat Biotech is seeking international manufacturing partners as it targets a billion doses of its COVID-19 vaccine each year, the company said on Sunday.

COVAXIN, the company's home-grown COVID-19 vaccine approved for emergency use in India, is one of two shots driving the country's massive vaccination programme.

But Bharat Biotech has struggled to boost output, missing supply commitments to the Indian government, which is also relying on a version of the AstraZeneca vaccine produced by the Serum Institute of India and Russia's Sputnik V vaccine.

On Sunday, the company rolled out the first batch of COVAXIN shots from a facility in Ankleshwar in western India that has the capacity to produce more than 10 million doses per month.

Bharat Biotech said it was exploring opportunities with its international partners who have expertise in commercial-scale manufacturing of inactivated viral vaccines.

"We want to ensure that Bharat Biotech can ably meet the demand for COVAXIN such that individuals across the country, and the globe, have access to the vaccine," chairman and managing director Krishna Ella said in a statement.

Last month, Health Minister Mansukh Mandaviya told parliament that Bharat Biotech would supply 25 million doses in July and 35 million in August, less than half what the government had initially expected.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-India-s-Bharat-Biotech-scouts-international-COVID-19-vaccine-partners-36272951/

McConnell: US has 'little or no leverage' to evacuate Americans, Afghan allies

 Senate Minority Leader Mitch McConnell (R-Ky.) on Sunday said the U.S. has "little or no leverage" to evacuate American citizens and Afghan allies from Afghanistan after U.S. troops withdraw on Aug. 31.

“We have little or no leverage to get our people out or our allies,” McConnell told host Chris Wallace on “Fox News Sunday.”

McConnell’s comments came after national security adviser Jake Sullivan told Wallace that the U.S. has “substantial leverage” to ensure American citizens and others can be safely evacuated from the country.

McConnell also raised concerns regarding American citizens and Afghan allies who choose to remain in the region after President Biden’s deadline, saying those individuals will become “either a potential victim or hostage.”

“Remember, the Taliban love taking hostages. They've done this before. It puts us in an extraordinarily difficult position,” he said.

He noted the difficulty the U.S. would have in extracting those individuals once U.S. forces leave, noting the landlocked nature of the country.

“Remember, Afghanistan is landlocked. There's only one way in by air and one way out by air. We don't have sort of friends in the neighborhood that would provide us the kind of intelligence that we would normally get, for example, in Syria or in Africa or in Yemen,” he said.

“It's going to be extremely difficult. We have very, very little leverage to extract additional Americans or Afghan allies from this landlocked country,” he added.

McConnell also slammed Biden's decision to pull U.S. troops from Afghanistan, calling it "one of the worst foreign policy decisions in American history."

https://thehill.com/homenews/sunday-talk-shows/569898-mcconnell-says-us-has-little-or-no-leverage-evacuate-americans-and

Fauci: US still planning booster shots after eight months, but 'flexible'

 Chief medical adviser Anthony Fauci said on Sunday the timeline of administering COVID-19 vaccine booster shots for fully-vaccinated Americans is "flexible" around the 8-month mark first suggested by U.S. officials.

“We're still planning on eight months. That was the calculation we made. This rollout will start on the week of September the 20th. But as we've said all along, Chuck, in the original statement, that's the plan that we have, but we are open to data as they come in,” Fauci told NBC’s Chuck Todd on “Meet The Press.”

Fauci noted that the booster shot rollout was still pending approval from the Food and Drug Administration (FDA) in addition to the Centers for Disease Control and Prevention’s (CDC) advisory committee. 

The booster shot recommendation by U.S. health officials came in part from Israel's decision to administer booster shots to its population after it became one of the first countries to reach high vaccinated levels.

On Friday, President Biden met with Israeli Prime Minister Naftali Bennett to talk its vaccination program among other agenda items. Biden said on Friday that the two had already spoken about booster shots, and he raised the question of whether the timeline between the second and third COVID-19 doses should be decreased.

“The question raised is: Should it be shorter than eight months?  Should it be as little as five months?  And that’s being discussed,” Biden said. 

 

Fauci said that officials were planning on keeping the timeline as is but noted it could be amended if more data was available.

“We're not changing it, but we are very open to new data as it comes in. We're going to be very flexible about it,” Fauci said on Sunday.

https://thehill.com/homenews/sunday-talk-shows/569901-fauci-us-still-planning-booster-shots-after-eight-months-but

FDA sees growing pressure to authorize vaccines for children under 12

Pressure on the Food and Drug Administration (FDA) is shifting to vaccine authorization for children under 12, now that the Pfizer vaccine has been fully approved for adults. 

With children going back to school and the delta variant raging, some experts and lawmakers are calling for the agency to act with more urgency and to clarify its timeline for authorizing a COVID-19 vaccine for children, given that none is currently available for those under 12. 

More than 100 House lawmakers wrote to the FDA last week asking for an update on its timeline for vaccines for children, given the current “alarming” situation. 

“The [FDA] seems to be oblivious to the urgency that millions of parents with young kids feel about vaccination,” Rep. Ro Khanna (D-Calif.), one of the leaders of the letter, tweeted on Wednesday. “Their communication has been very poor. Parents need a timeline.”

Lee Savio Beers, the president of the American Academy of Pediatrics (AAP), also wrote to the FDA earlier this month, pressing it to move “aggressively,” to authorize vaccines for children “as soon as possible.”

One complicating factor is the potential for rare cases of heart inflammation, known as myocarditis, linked to the vaccine in younger people. 

Beers wrote that there is “justifiable concern,” about such cases, but that they are “extremely rare,” and are likely to occur within four weeks of vaccination. 

And on the flip side, the delta variant is causing a surge in COVID-19 cases. While children generally fare better than older people, they are not totally immune. 

The AAP reported 180,000 new COVID-19 cases among children and adolescents in the week ending Aug. 19. 

“In our view, the rise of the Delta variant changes the risk-benefit analysis for authorizing vaccines in children,” Beers wrote. 

In an interview, Khanna said there was added “confusion” on the timeline this week when Francis Collins, the director of the National Institutes of Health, and Anthony Fauci, seemingly gave differing estimates for when an authorization could occur.  

Collins told NPR: “I don't see the approval for kids 5 to 11 coming much before the end of 2021.” 

Fauci, on the other hand, told NBC the authorization for children could come “hopefully by the mid-late fall and early winter.”

“There needs to be a briefing of Congress of what is the timeline and what is it that they’re waiting on,” Khanna told The Hill. 

Asked to clarify Collins and Fauci’s timelines, NIH spokesperson Renate Myles said the two timetables are “roughly” the same. “Dr. Collins said (in various iterations) that he sees approvals for vaccines for kids 5 to 11 coming before the end of the year, although not much before then,” Myles wrote in an email. “Mid-fall or early winter (November/December) is roughly the same estimation, just a different choice of words.”

Data from trials in children still need to be submitted to the FDA before an authorization could occur. Collins told NPR that Pfizer data could come in “by the end of September.”

Peter Marks, a top FDA official, likewise said earlier this month that data for 5- to 11-year-olds could come “early in the fall,” but “it will take a few weeks at least to review them.” The number of safety questions could determine how long the process takes, he said. 

“If there are any kind of safety issues that we have any concerns about, we may have to go back to an advisory committee because we want to make sure that when these things are authorized, that people feel really comfortable that they can be used,” Marks said, speaking at an event hosted by the COVID-19 Vaccine Education and Equity Project. 

Data for children under 5 are expected to come in later than data for those 5-11, perhaps “later this fall to early winter,” Marks said. 

“We are very aware that people are very anxious to get their children vaccinated,” Marks acknowledged. “We just have to make sure that when we put our imprimatur, our FDA either emergency use authorization or approval on something, that we really feel confident that it has met our standards for safety, effectiveness and quality.”

The stakes were illustrated on Thursday by a letter from Mark Wietecha, CEO of the Children’s Hospital Association. “With pediatric volumes at or near capacity and the upcoming school season expected to increase demand, there may not be sufficient bed capacity or expert staff to care for children and families in need,” he warned in the letter to President Biden. 

https://thehill.com/policy/healthcare/569633-fda-sees-growing-pressure-to-authorize-vaccines-for-children-under-12

The Danger of Expanding Medicare

 Moderate Democrats like Sens. John Breaux of Louisiana and Bob Kerrey of Nebraska once favored gradually raising the Medicare eligibility age to help ensure the program’s financial sustainability. But few of them are left in Congress. Today the “moderate” Democratic position is that the eligibility age should be lowered as an alternative to establishing a single-payer system. Senate Finance Committee Chairman Bernie Sanders also favors opening Medicare to everyone over 60, but as a step toward single payer.

The Democrats’ $3.5 trillion Senate budget plan allows the final legislation to lower the eligibility age. President Biden’s budget also endorses the plan, which would cost $200 billion over 10 years and add more than 20 million younger sexagenarians to the 63 million seniors and disabled beneficiaries who already rely on the program. It would also worsen the program’s finances, unnecessarily replace private dollars with tax dollars, and hurt doctors and other providers of medical services.

Medicare’s Part A trust fund, which pays for hospital benefits, is already projected to be insolvent by 2026. Even without expansion, Medicare spending is projected nearly to double over the next 10 years. Congress’s first priority should be to strengthen the program’s finances so that vulnerable seniors can continue to access life-saving health care.

Democrats claim expanding Medicare is necessary to reduce the number of uninsured Americans. But lowering Medicare’s eligibility age is an inefficient way to accomplish that. Two-thirds of Americans 60 to 64 already have private coverage through an employer or the individual market. The plan could move as many as 11.7 million people with employer coverage and 2.4 million people with individual coverage onto Medicare’s rolls, shifting the bill to taxpayers without expanding coverage. Only 8% of the newly eligible population, or 1.6 million people, are currently uninsured. Two-thirds are already eligible for Medicaid or exchange subsidies, 15% have access to employer-provided coverage, and 7% are illegal aliens ineligible for Medicare.

Private payers pay substantially higher rates to hospitals and physicians, in some cases as much as doubling Medicare’s hospital rates. Expanding government coverage at the expense of private coverage will make it harder for providers to continue shifting costs to higher-paying private patients. The result will be longer lines, less care, and decreased incentive for innovation in treatment and care.

Bobby Jindal served as the 55th Governor of Louisiana from 2008 to 2016. Jindal previously served as a member of the U.S. House of Representatives and Chairman of the Republican Governors Association.

https://www.wsj.com/articles/expanding-medicare-for-all-socialized-medicine-health-insurance-cost-age-requirement-11629900715

Please Reevaluate the Data on Convalescent Plasma for COVID-19

 As the Delta variant surges, we have a therapy that is inexpensive, available, potentially effective when used correctly, and underused in the treatment of COVID-19. We are referring to COVID-19 convalescent plasma (CCP), a form of antibody therapy derived from donors who have recovered from COVID-19. When CCP was first deployed, many of us anticipated that it would be followed by powerful new antiviral drugs for patients hospitalized with COVID-19. Unfortunately, such drugs have not materialized. We also anticipated that with highly effective vaccines, the pandemic would have ebbed by now. That too has not happened. Instead, the country has again reported facing more than 1,000 deaths in a single day and has limited therapeutic options.

Recent History of COVID-19 Convalescent Plasma

To understand the situation with CCP we need to review some history. In March 2020, the U.S. became the first country to make CCP readily available. The FDA allowed CCP use first through case-by-case requests from doctors, and next through an expanded access program (EAP) coordinated by the Mayo Clinic, which carefully monitored CCP use. The rationale for CCP use was threefold: convalescent plasma worked in prior epidemics, antibody from recovered patients had strong antiviral activity, and plasma was known to be remarkably safe. Most importantly, no other specific therapy was available.

By mid-summer 2020, almost 100,000 patients had been treated with CCP under the aegis of the EAP, and strong evidence emerged that it was safe and effective when used early in hospitalization, leading the FDA to issue, in August 2020, an emergency use authorization. The Mayo Clinic and FDA, each independently analyzing the EAP data, found that mortality was lower in CCP-treated patients if units with high antibody content were administered before severe disease had developed.

The deployment of CCP -- beginning within a month of the first pandemic surge -- was an American success story. It was driven by a grassroots effort of physician networks, blood banks, community organizers, and individual donors who self-organized to study and promote CCP use under careful oversight by the FDA. In the months that followed, several observational studies and small randomized trials reported that CCP use was associated with reduced mortality, and by October 2020, CCP was used in approximately 40% of all hospital admissions for COVID-19. Tragically, as with so much in COVID-19, CCP was politicized, creating a cloud from which it has yet to fully emerge.

In the fall and winter 2020-21, three randomized controlled trials from India, Argentina, and the U.K. evaluated treatment in hospitalized patients with severe disease. They each reported that CCP had no effect on overall mortality, despite suggestions of efficacy in some subgroups. In contrast, another randomized trial from Argentina showed that early administration of CCP to elderly outpatients substantially prevented disease progression from mild to severe. Unfortunately, this result was less influential in the U.S., where the FDA had limited CCP use to hospitalized patients. Consequently, there was a dramatic decline in CCP use, and by March 2021, only about 10% of hospitalized COVID-19 patients received CCP. We have estimated that this retreat from CCP use was associated with 30,000 excess deaths from December 2020 to March 2021. In late spring of 2021, a double-blinded, placebo-controlled trial from a Columbia University-Brazil collaboration and a large analysis of real-world data from HCA Healthcare reported that CCP use was associated with statistically significant reductions in mortality. These results arrived at a time when vaccines seemed to have vanquished the epidemic and thus received little attention.

Efficacy of COVID-19 Convalescent Plasma

Why is the evidence on CCP efficacy so mixed? The answer lies in the complexity of antibody action and the nature of CCP itself. Antibody therapies are effective only when given early in the course of disease and when the infused plasma contains enough antibody to effectively contain the virus. In COVID-19, the initial viral phase can trigger an over-exuberant inflammatory response later in the course of illness and is often the process responsible for COVID-19-associated deaths. Early administration of CCP with sufficient antibody reduces the amount of virus in the patient, reducing the chance of progression to life-threatening disease. By the time the inflammatory response in COVID-19 has taken hold, antibody therapy is less likely to be helpful.

Tragically, but understandably, given the hectic early days of the pandemic, several randomized trials were designed without taking these principles into consideration. Most trials included substantial numbers of patients in advanced stages of disease when the inflammatory response was dominant. Some trials also used plasma with insufficient antibody content. These trials might have been anticipated to fail, and when they did, they created a circular logic that discouraged plasma use. Since then, we have learned that local plasma is most effective, providing another explanation for why some trials using nationally sourced plasma failed to show efficacy. The reliance on trials for decision-making in clinical medicine is now so powerful that when these trials, which tested CCP in suboptimal cases, delivered the message that CCP was ineffective, plasma use dropped substantially.

Take a Second Look at the Data

As our country confronts a rapidly accelerating Delta variant surge, there is no time to redo clinical trials. We ask that physicians reevaluate the available data, review the guidance for use, and consider using CCP early in hospitalization, ideally as soon as the decision to admit has been made. CCP lacks the toxicity of remdesivir (Veklury), or the risks of steroid use, which include superinfections.

Some physicians may respond by pointing out that the recently published C3PO trial of early CCP therapy did not show that CCP prevented disease progression. However, a close examination of the trial design and outcome does not support that conclusion. The trial design was flawed in that it included in the primary outcome patients admitted during the index visit and considered unrelated emergency room visits as outcome events. If these patients are removed from the analysis, the numbers show that the group receiving CCP had a 35% lower chance of progressing to hospitalization (see our critique of the study). The study also shows that two other important outcomes -- dyspnea and worsening of disease on a five-point scale after day 1 -- were significantly less frequent in the plasma arm.

In most hospitalized patients, the disease process may be too advanced for CCP to be effective. Some patients, particularly those who are delayed in producing their own antibody response, may still benefit late in illness. Among people with blunted antibody responses -- such as some hematologic malignancy patients, transplant recipients, and some being treated for auto-immune disorders -- CCP may be helpful at any point in the disease course. This is included in FDA guidance for CCP use.

Individuals at high risk for COVID-19 progression should be treated with monoclonal antibodies as outpatients (the FDA has only authorized outpatient use) and, if the disease progresses, should be seen in a hospital where CCP is available.

Overall, we estimate that CCP may have saved close to 100,000 lives during the pandemic in the U.S. alone. If physicians heed FDA recommendations -- use CCP with adequate antibody levels early in hospitalization – the toll of the Delta variant could be lessened.

The authors comprise the leadership group on the COVID-19 Convalescent Plasma Project. Arturo Casadevall, MD, PhD, is a professor of molecular microbiology and immunology at the Johns Hopkins School of Public Health. Brenda Grossman, MD, MPH, is a professor of pathology & immunology and medicine at Washington University in St. Louis. Jeffrey Henderson, MD, PhD, is an associate professor of medicine and Molecular Microbiology at Washington University in St. Louis. Michael Joyner, MD, is a professor of anesthesiology at the Mayo Clinic. Nigel Paneth, MD, MPH, is an emeritus university distinguished professor of epidemiology and biostatistics and pediatrics at Michigan State University. Liise-anne Pirofski, MD, is a professor at Albert Einstein College of Medicine & Montefiore Medical Center. Shmuel Shoham, MD, is associate professor of medicine at Johns Hopkins School of Medicine.

Disclosures

Casadevall disclosed participation on the scientific advisory board of SAb Biotherapeutics; receiving payments as a speaker for Ortho Diagnostics; and payments for data and safety monitoring board (DSMB) work from Bristol Myers Squibb. Shoham disclosed receiving payments for consulting from Adagio, Celltrion, and Immunome; payments for DSMB work from Adamis, Intermountain Health, and Karyopharm; and research grants from Ansun.

https://www.medpagetoday.com/opinion/second-opinions/94256

Past Infection May Better Protect Against Delta Than Vaccine, but …

 A prior infection from COVID-19 was more protective than vaccine-induced immunity in reducing the risk of infection and symptomatic illness from the Delta variant, according to a retrospective observational study from Israel.

Those who received both doses of the Pfizer/BioNTech vaccine in January or February of this year had a 13.06-fold increased risk (95% CI 8.08-21.11) of SARS-CoV-2 infection with the Delta variant compared to those who had COVID-19 during the same time period, reported Sivan Gazit, MD, MA, of Maccabi Healthcare Services in Tel Aviv, and colleagues.

Vaccine-induced immunity was also associated with a 27-fold increased risk for symptomatic infection (95% CI 12.7-57.5) compared with symptomatic reinfection (P<0.001), the researchers wrote in a paper published on the preprint server medRxiv, which has not undergone peer-review.

Among people with prior infection, a single dose of the vaccine conferred more protection against reinfection compared with no vaccination at all (OR 0.53, 95% CI 0.3-0.92).

But experts cautioned that these results shouldn't encourage people to go out and get infected. Robert Schooley, MD, of the University of California San Diego, told MedPage Today that waiting around to get infected with the hopes of gaining natural immunity puts people at risk of infection without a baseline level of protection.

"Unvaccinated people who get infected are where we see the deaths occurring," he wrote in an email. "Putting yourself at risk of dying to have 'natural' immunity is not a great tradeoff."

Schooley also noted that these findings are limited due to a potential underestimate of asymptomatic infections. COVID-19 infections in this study were detected upon health visits via PCR testing. Because people with asymptomatic infection are typically less likely to get a test, this study may have been skewed more towards symptomatic patients.

"The more symptomatic your infection is, the more likely you are to mount a brisk immune response," Schooley pointed out.

This was the largest real-world study to compare immunity to SARS-CoV-2 derived from natural infection versus vaccination, the researchers said.

The retrospective study used a large healthcare database in Israel and included patients ages 16 and older in three groups: SARS-CoV-2-naive individuals who were fully vaccinated; previously infected people who were unvaccinated; and previously infected people who received a single dose of the vaccine. Vaccination or infections occurred in January or February. Patients were followed from June to August -- the same time as the surge of cases from the Delta variant in Israel.

The researchers adjusted for covariates including age, sex, socioeconomic status, and comorbidities, including cardiovascular disease, hypertension, diabetes, kidney disease, obstructive pulmonary disease, immunocompromised conditions, and cancer.

Nearly 674,000 fully vaccinated people were included in the study. In the groups with previous infection, about 63,000 were unvaccinated, and 42,000 had received one dose.

Natural immunity appeared more protective against hospitalization, with eight hospitalizations in the vaccine immunity cohort, and one in the natural immunity cohort.

In a separate analysis that compared vaccine and natural immunity regardless of the time of infection, fully vaccinated patients had a higher risk of infection (OR 5.96, 95% CI 4.85-7.33) and symptomatic disease (OR 7.13, 95% CI 5.51-9.21).

There were no COVID-related deaths reported in any of the cohorts.

Because the Delta variant was the most common source of infection during the study period, these results cannot be translated to immunity against other strains, Gazit's group said. Additionally, they recognized that this study may have underestimated asymptomatic cases, and that the findings do not apply to those who received a vaccine other than Pfizer's.

Alessandro Sette, DSc, of the La Jolla Institute for Immunology in California, who was not involved in this study, emphasized that these findings "should not be interpreted as saying, 'if you have already been infected, don't get vaccinated.'"

"People who have been infected still get a benefit -- for themselves and for society -- by getting vaccinated, and one shot of vaccine is sufficient to achieve that," Sette said. (CDC recommends a two-dose series for the mRNA vaccines or the single-shot Johnson & Johnson vaccine regardless of prior infection status.)

Disclosures

There was no external funding used to conduct this research.

Gazit and colleagues did not disclose any potential conflicts of interest.

Primary Source

medRxiv

Source Reference: Gazit S, et al "Comparing SARS-CoV-2 natural immunity to vaccine-induced immunity: reinfections versus breakthrough infections" medRxiv 2021; DOI: 10.1101/2021.08.24.21262415.

https://www.medpagetoday.com/infectiousdisease/covid19/94258