Concerns as India to roll out home-grown vaccine

 A homegrown coronavirus vaccine will be rolled out in India from Saturday even though clinical trials haven't been completed. But the government insists it will be safe and effective.

The All India Drug Action Network (AIDAN), an independent watchdog, led a chorus of concern from experts saying it was "shocked" and "baffled" by the emergency approval of Covaxin.

India has been hit hard by the virus, logging the second-highest number of COVID-19 infections globally with more than 10.5 million cases, and over 150,000 deaths—behind only the United States and Brazil.

In early January New Delhi greenlighted Covishield, a version of AstraZeneca and Oxford University's shot made by India's Serum Institute, the world's largest vaccine manufacturer.

But it also gave "emergency approval" to Covaxin, developed in India by Bharat Biotech and the Indian Council of Medical Research, even though phase 3 human trials were yet to be completed.

Authorities stated—without releasing supporting data—that Covaxin might work better against new COVID-19 strains than other vaccines that use different technologies.

According to Prabir Chatterjee, a community medicine specialist in West Bengal, the lack of data was causing "a lot of upset among doctors and very senior doctors and scientists."

"I would guess that the Bharat Biotech vaccine, after it has been evaluated, may be the best, the cheapest and the most practical for developing countries," he told AFP.

"But... I don't think we should jumpstart the process by using it before it has been proved."

The main opposition Congress party accused the government of putting lives at risk. The health minister of one state, Chhattisgarh, has said the Bharat vaccine is "not safe" to deploy.

Critics suspect that the swift approval was motivated by Prime Minister Narendra Modi's protectionist push for "self-reliance", and by the desire to save money.

The government responded to the criticism by saying the vaccine is "110-percent safe".

Husband and wife

Privately owned Bharat Biotech, set up in 1996 by husband and wife Krishna Ella and Suchitra Ella, is an established player in inoculations.

It has delivered over three billion vaccines for diseases worldwide including Zika and Japanese Encephalitis and an ultra-cheap shot for Hepatitis B.

The firm intends to supply Covaxin to other countries including Brazil.

But activists have accused the firm of cutting corners and breaching rules in conducting trials in India.

In the central city of Bhopal, Bharat's local partner the People's College of Medical Sciences and Research Centre paid 750 rupees ($8) each to 1,722 recruits.

Rajesh Kapur, vice chancellor of the private hospital, said it adhered to all proper protocols and ethical practices, including counselling and monitoring subjects, seeking their informed consent, and arranging care in case of health complications.

But 10 participants AFP spoke with, several of whom are illiterate, said they had not been properly informed.

Some said they were not given any documentation or briefing, while others said they were told they were being given a vaccine that would soon become mandatory nationwide.

Being informed of risks and signing consent forms have been mandatory since the government tightened the rules of drug testing—a booming industry in India—following a number of scandals.

Illiterate wage labourer Mannsingh Parihar, 70, said he and four others were driven to the hospital on December 21 and given the injection.

"They did not say a word (about it being a trial). They gave the injection and money and asked me to go," he told AFP.

Similar allegations are echoed by other participants interviewed by Indian media and by activists.

"No informed consent was taken, no adverse events have been recorded, no monitoring and follow-up is being done," activist Rachna Dhingra said.

Public concern was fueled by the widely reported death of one trial participant, nine days after being injected.

A post-mortem said the cause of death was suspected poisoning and Bharat said the death appeared to be "unrelated" to the trial dosing.

A detailed email questionnaire from AFP to Bharat on the claims was not answered.

The Bhopal controversies have been a lightning rod for criticism across the nation about the trials and the wisdom of rushing the vaccine's roll-out.

"There seems to be clear misses in the way these trials have been conducted," said Anant Bhan, an expert on bioethics and health policy.

https://medicalxpress.com/news/2021-01-india-home-grown-vaccine.html

‘Tourists’ flying to Florida to score COVID-19 vaccine early

 Seniors are jetting off to Florida — but it’s not warm weather they’re seeking.

The state was one of the first to begin offering vaccines to people ages 65 and older, by executive order on Dec. 23. According to local news reports in Florida, the state is seeing an influx of “vaccine tourists,” out-of-state travelers hoping to jump ahead in line for the coronavirus vaccine.

It’s not just impatient Americans scurrying to the front. Momentum Jets, a Toronto-based private airline, told the Wall Street Journal that wealthy Canadians have been willing to pay between $25,000 to $80,000 for same day, round-trip flights with the carrier.

A spokesperson for Travel Secure Inc., a travel insurance brokerage agency, added that some 30% of clientele booked flights for the Southern US during the month of November — believing those folks had gone to receive their first dose of vaccine or set an appointment for one.

Governor Ron DeSantis insisted on Tuesday that the state would not allow one-time visitors arriving for the vaccine, clarifying that so-called “snowbirds,” or dual-state residents who weather their winters in the South, would be permitted, the Orlando-Sentinel reported.

“We’re not doing any tourists,” he said during a press conference, broadcast from Florida retirement community the Villages.

Nearly 800,000 have already received the first poke, according to the Florida Department of Health, where almost 500,000 of them were part of the 65 and over age group.

The trend is putting the squeeze on already strained hospitals, clinics and local health officials, who complained of a lack of support from the state and federal governments in terms of vaccine implementation.

“It’s very unstable and very frustrating for the population,” Dr. Mary Jo Trepka, an
epidemiologist at Florida International University, told WSJ. “There are many worried people who want a vaccine and can’t get it.”

In Miami, the Jackson Health System, a network of more than 40 hospitals and health centers, stated they’re taking all measures to verify state residency among vaccine recipients, but they won’t turn away part-time residents, either.

“Regardless of where someone lives, if they are spending time in our community — on our beaches, in our restaurants, in our malls — they can be spreaders of this virus,” they said in a statement.

The DOH stressed that vaccine tourism, those who “come into Florida for one day to receive the vaccine and leave the next,” is prohibited. They’re asking that “all suspected incidents … immediately” be reported to a local health department branch.

When news broke earlier this week that Yanina Latorre, an Argentinian television personality, had enlisted fans to help bring her 80-year-old mother to Miami for the vaccine, Miami’s Mayor Francis Suarez vowed to take action.

“I’m totally in disagreement with people from out of town coming and getting the

vaccine before City of Miami residents,” said Mayor Suarez. “I will look
into all legal options to prevent this from happening.”

https://nypost.com/2021/01/15/people-are-flying-to-florida-for-covid-19-vaccine/

Studying and treating COVID-19's long-term impact

 COVID-19 has wreaked havoc around the globe, causing nearly 2 million deaths worldwide, including more than 380,000 fatalities in the United States alone. While much has been learned about the disease in the year since it was first detected, its long-term effects on the health of COVID-19 survivors may take years to understand. A major effort to gain that understanding is about to begin, as Rush University Medical Center and partners across the country launch a nationwide study of patients who have been infected with the COVID-19 virus.

INSPIRE (Innovative Support for Patients with SARS COV-2 Infections Registry) is a federal Centers for Disease Control and Prevention-funded project led by Rush, along with the University of Washington, Yale New Haven Health and a trans-continental team that includes the University of Texas Health Science Center at Houston (aka UTHealth), the University of Texas Southwestern Medical Center (UT Southwestern), UCLA, the University of California, San Francisco and Thomas Jefferson University. The study will track 3600 individuals with new COVID-19 symptoms who have been diagnosed with the disease in the preceding four weeks and 1200 people without COVID-19 to assess the long-term outcomes of infections with SARS CoV-2, the virus that causes COVID-19, on various age groups over a two-year period. More details can be found here: https://clinicaltrials.gov/ct2/show/NCT04610515

With a philosophy that views study participants as part of the team -- ensuring patient involvement, engagement and control over their data -- researchers will look closely at COVID-19 survivors' health care utilization, ongoing clinical events, and physical and mental function, including neurocognitive function and fatigue.

INSPIRE participants will register using the Hugo platform, a health data system that leverages individuals' legal right to access to their own health information and collects health data on their behalf while maintaining the highest degree of confidentiality. This arrangement will allow essential, large-scale data gathering.

"This disease will be with us for years to come, and understanding the impact on the health of survivors will be essential to our understanding of how to treat it," said Dr. Bala Hota, chief analytics officer at Rush and an infectious disease expert. "This work will provide the foundation for our long-term understanding of the ongoing impact of COVID-19."

"These insights are crucial for understanding the complexities of these impacts so that we can improve the quality of clinical care for our patients," added Dr. Joann Elmore, principal investigator at the UCLA site, professor of medicine in the Department of Medicine at the David Geffen School of Medicine and professor of health policy and management at the Fielding School of Public Health.

New Rush clinic focuses on post-COVID care

The study coincides with Rush's launch of a new post-COVID care clinic at the Medical Center. The clinic's patients work closely with a patient navigator who will help coordinate care and connect them with a team of expert providers who will help patients find their way through the many unknowns of life after COVID-19.

"What is both surprising and highly unpredictable is determining who will have long-lasting effects from COVID-19 and what types of symptoms they will continue to have long after they no longer have the disease itself," said Dr. Monnie Wasse, director of the post-COVID clinic and vice chairperson and director of interventional nephrology in the Medical Center's Department of Internal Medicine. "Right now, that is a key question we are asking ourselves as health care professionals. Between our clinic and this research, we will be advancing our knowledge rapidly."

Enrollment and recruitment for INSPIRE is now underway. To enroll, please visit the INSPIRE website. Information will be gathered through ongoing surveys and will not require participants to see a doctor.

https://www.eurekalert.org/pub_releases/2021-01/rumc-sat011321.php

Population density, virus strains affect how regions can resume normalcy

 As a new, apparently more transmissible version of the virus that causes COVID-19 has appeared in several countries, new research finds that the transmissibility of viral strains and the population density of a region will play big roles in how vaccination campaigns can help towns and cities return to more normal activities.

The findings suggest that directing vaccines toward densely populated counties would help to interrupt transmission of the disease. Current vaccination distribution plans don't take density into account.

Tony Ives at the University of Wisconsin-Madison and Claudio Bozzuto of the independent data research company Wildlife Analysis GmbH studied the spread of COVID-19 in the U.S. at the start of the pandemic, before people changed their behavior to avoid the disease. This let them uncover factors that may affect the transmission of COVID-19 when masking and physical distancing start to wane and behavior once again resembles the pre-pandemic normal.

"We wanted to get at two things: the first was to try and understand what the dynamics were very early in the pandemic. If we need a vaccination program in place that lets people act normally, then we need to understand the state under those conditions," says Ives, a professor of integrative biology at UW-Madison. "The second was trying to get at a fairly small spatial scale of counties instead of states."

Parsing out county-by-county data from 39 states through May 23, 2020, Ives and Bozzuto found that the higher a county's population density, the more readily SARS-CoV-2, the virus responsible for COVID-19, spread from person to person. This county-level spread is ultimately quantified in the basic reproduction number of the virus, a measure of the average number of people an infected person goes on to infect.

The researchers also found compelling evidence that viral strain matters. Ives and Bozzuto saw that the regions hosting a greater proportion of strains containing a mutation called G614 experienced greater viral spread, a finding supported by other research showing that this strain could be transmitted more readily.

While the G614 mutant is unrelated to B.1.1.7, a strain first identified in the United Kingdom that appears to be spreading more easily right now, the new study reflects the importance that viral strain can play in a local area's overall disease spread.

"We found a clear pattern in the spread rate due to different strains," says Bozzuto. "Our approach was novel because we went directly to the community level to ask, 'Can we see any patterns in the data without making assumptions about individual behavior, including strain-related transmissibility and pathogenicity?'"

To track the rate of viral spread, Ives and Bozzuto worked with the number of people who died of COVID-19 last spring. When testing was limited at the beginning of the pandemic, deaths much more accurately tracked COVID-19 transmission. As long as a relatively constant proportion of infected people die from the disease, data on how deaths increase over time will be directly proportional to the overall rate of spread.

Population density predicted a considerable amount of the difference in the rate of viral spread from county to county during the time period the researchers studied. Counties with low or moderate density did not have high rates of infection spread, though lower transmission rates do not necessarily protect a region from eventually seeing high case counts.

Location explained an even greater fraction of the spread in the researchers' model. Regions within a few hundred miles of one another had similar transmission rates. This regional similarity might have been caused in part by similar public health responses in neighboring counties.

But Ives and Bozzuto also found evidence that regional differences in viral strains explained why neighboring counties looked similar. For example, the low proportion of G614 mutants in the Northwest and Southeast was associated with lower transmission rates.

The researchers investigated several other factors -- such as prevalence of obesity and diabetes, socioeconomic status, and political affiliation -- and found that none of them contributed significantly to the rate of spread of COVID-19 at the very start of the epidemic. Although these factors may affect how susceptible individuals and populations are to complications from the disease, they didn't appear to affect the transmission of the virus from person to person.

The new findings were published in the journal Communications Biology on Jan. 5. Ives and Bozzuto say their work can help public health officials decide where vaccines would do the most good.

"Vaccination programs should consider potential spread rate in different areas. The main driver that will be important is density," says Ives. "From an epidemiological perspective, we would argue that metropolitan areas should be targeted because the level of vaccination or acquired immunity has to be higher than in largely rural areas."

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This work was supported by NASA (grant 80NSSC20K0282).

https://www.eurekalert.org/pub_releases/2021-01/uow-pda011421.php

Rapid blood test identifies COVID-19 patients at high risk of severe disease

 One of the most vexing aspects of the COVID-19 pandemic is doctors' inability to predict which newly hospitalized patients will go on to develop severe disease, including complications that require the insertion of a breathing tube, kidney dialysis or other intensive care. Knowledge of a patient's age and underlying medical conditions can help predict such outcomes, but there are still surprises when younger, seemingly healthier patients suffer severe complications that can lead to death.

Now, scientists at Washington University School of Medicine in St. Louis have shown that a relatively simple and rapid blood test can predict -- within a day of a hospital admission -- which patients with COVID-19 are at highest risk of severe complications or death.

The study, published Jan. 14 in JCI Insight, involved nearly 100 patients newly admitted to the hospital with COVID-19.

The blood test measures levels of mitochondrial DNA, a unique type of DNA molecule that normally resides inside the energy factories of cells. Mitochondrial DNA spilling out of cells and into the bloodstream is a sign that a particular type of violent cell death is taking place in the body.

"Doctors need better tools to evaluate the status of COVID-19 patients as early as possible because many of the treatments -- such as monoclonal antibodies -- are in short supply, and we know that some patients will get better without intensive treatments," said co-senior author Andrew E. Gelman, PhD, the Jacqueline G. and William E. Maritz Endowed Chair in Immunology and Oncology in the Department of Surgery.

"There's so much we still don't understand about this disease," he added. "In particular, we need to understand why some patients, irrespective of their ages or underlying health in some cases, go into this hyperinflammatory death spiral. Our study suggests that tissue damage may be one cause of this spiral, since the mitochondrial DNA that is released is itself an inflammatory molecule."

The researchers said the test could serve as a way to predict disease severity as well as a tool to better design clinical trials, identifying patients who might, for example, benefit from specific investigational treatments. They also said they would like to evaluate whether the test could serve as a way to monitor the effectiveness of new therapies. Presumably, effective treatments would lower mitochondrial DNA levels.

"We will need larger trials to verify what we found in this study, but if we could determine in the first 24 hours of admission whether a patient is likely to need dialysis or intubation or medication to keep their blood pressure from dropping too low, that would change how we triage the patient, and it might change how we manage them much earlier in the disease course," said co-senior author Hrishikesh S. Kulkarni, MD, an assistant professor of medicine.

The researchers, including co-first authors Davide Scozzi, MD, PhD, a staff scientist, and Marlene Cano, PhD, a postdoctoral research scholar, evaluated 97 patients with COVID-19 at Barnes-Jewish Hospital, measuring their mitochondrial DNA levels on the first day of their hospital stays. They found that mitochondrial DNA levels were much higher in patients who eventually were admitted to the ICU, intubated or died. The researchers found this association held independently of a patient's age, sex and underlying health conditions.

On average, mitochondrial DNA levels were about tenfold higher in patients with COVID-19 who developed severe lung dysfunction or eventually died. Those with elevated levels were almost six times more likely to be intubated, three times more likely to be admitted to the ICU and almost twice as likely to die compared with those with lower levels.

Further, the test predicted outcomes as well as or better than existing markers of inflammation currently measured in patients hospitalized with COVID-19. Most other markers of inflammation measured in patients with COVID-19, including those still under investigation, are general markers of systemic inflammation, rather than inflammation specific to cell death, according to the researchers.

"Viruses can cause a type of tissue damage called necrosis that is a violent, inflammatory response to the infection," Gelman said. "The cell breaks open, releasing the contents, including mitochondrial DNA, which itself drives inflammation. In COVID-19 patients, there has been anecdotal evidence of this type of cell and tissue damage in the lung, heart and kidney. We think it's possible that measures of mitochondrial DNA in the blood may be an early sign of this type of cell death in vital organs."

The researchers also emphasized that the test is quick and straightforward to perform in most hospital settings because it uses the same machinery that processes the standard PCR test for COVID-19. The method they developed allows mitochondrial DNA levels to be quantified directly in the blood. Without requiring intermediate steps to extract the DNA from the blood, the technique returned results in less than an hour.

Before they can apply for approval from the Food and Drug Administration (FDA), the scientists will need to verify that the test is accurate in a larger multi-center trial. They have plans to expand the research to more sites.

The study utilized samples obtained from the School of Medicine's COVID-19 biorepository, which was developed by co-authors Jane O'Halloran, MD, PhD, an assistant professor of medicine; Charles Goss, PhD, an instructor in biostatistics; and Phillip Mudd, MD, PhD, an assistant professor of emergency medicine.

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This work was supported by the Barnes Jewish Hospital Foundation; the Children's Discovery Institute; the National Institutes of Health (NIH), grant numbers, R01HL094601, P01AI116501 and K08HL148510; and the Washington University Institute of Clinical and Translational Sciences (ICTS) COVID-19 Research Program, which is funded by the National Center for Advancing Translational Sciences (NCATS) of the NIH, grant number UL1TR002345.

Scozzi D, Cano M, et al. Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19. JCI Insight. Jan. 14, 2021.

https://www.eurekalert.org/pub_releases/2021-01/wuso-rbt011521.php

DNA test can quickly identify pneumonia in patients with severe COVID

 Researchers have developed a DNA test to quickly identify secondary infections in COVID-19 patients, who have double the risk of developing pneumonia while on ventilation than non-COVID-19 patients.

For patients with the most severe forms of COVID-19, mechanical ventilation is often the only way to keep them alive, as doctors use anti-inflammatory therapies to treat their inflamed lungs. However, these patients are susceptible to further infections from bacteria and fungi that they may acquire while in hospital - so called 'ventilator-associated pneumonia'.

Now, a team of scientists and doctors at the University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, led by Professor Gordon Dougan, Dr Vilas Navapurkar and Dr Andrew Conway Morris, have developed a simple DNA test to quickly identify these infections and target antibiotic treatment as needed.

The test, developed at Addenbrooke's hospital in collaboration with Public Health England, gives doctors the information they need to start treatment within hours rather than days, fine-tuning treatment as required and reducing the inappropriate use of antibiotics. This approach, based on higher throughput DNA testing, is being rolled out at Cambridge University Hospitals and offers a route towards better treatments for infection more generally. The results are reported in the journal Critical Care.

Patients who need mechanical ventilation are at significant risk of developing secondary pneumonia while they are in intensive care. These infections are often caused by antibiotic-resistant bacteria, and are hard to diagnose and need targeted treatment.

"Early on in the pandemic we noticed that COVID-19 patients appeared to be particularly at risk of developing secondary pneumonia, and started using a rapid diagnostic test that we had developed for just such a situation," said co-author Dr Andrew Conway Morris from Cambridge's Department of Medicine and an intensive care consultant. "Using this test, we found that patients with COVID-19 were twice as likely to develop secondary pneumonia as other patients in the same intensive care unit."

COVID-19 patients are thought to be at increased risk of infection for several reasons. Due to the amount of lung damage, these severe COVID-19 cases tend to spend more time on a ventilator than patients without COVID-19. In addition, many of these patients also have a poorly-regulated immune system, where the immune cells damage the organs, but also have impaired anti-microbial functions, increasing the risk of infection.

Normally, confirming a pneumonia diagnosis is challenging, as bacterial samples from patients need to be cultured and grown in a lab, which is time-consuming. The Cambridge test takes an alternative approach by detecting the DNA of different pathogens, which allows for faster and more accurate testing.

The test uses multiple polymerase chain reaction (PCR) which detects the DNA of the bacteria and can be done in around four hours, meaning there is no need to wait for the bacteria to grow. "Often, patients have already started to receive antobiotics before the bacteria have had time to grow in the lab," said Morris. "This means that results from cultures are often negative, whereas PCR doesn't need viable bacteria to detect - making this a more accurate test."

The test - which was developed with Dr Martin Curran, a specialist in PCR diagnostics from Public Health England's Cambridge laboratory - runs multiple PCR reactions in parallel, and can simultaneously pick up 52 different pathogens, which often infect the lungs of patients in intensive care. At the same time, it can also test for antibiotic resistance.

"We found that although patients with COVID-19 were more likely to develop secondary pneumonia, the bacteria that caused these infections were similar to those in ICU patients without COVID-19," said lead author Mailis Maes, also from the Department of Medicine. "This means that standard antibiotic protocols can be applied to COVID-19 patients."

This is one of the first times that this technology has been used in routine clinical practice and has now been approved by the hospital. The researchers anticipate that similar approaches would benefit patients if used more broadly.

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This study was funded by the National Institute for Health Research Cambridge Biomedical Research Centre.

https://www.eurekalert.org/pub_releases/2021-01/uoc-dtc011421.php

Cancer biotech Immunocore files for a $100 million US IPO

 Immunocore Holdings, Phase 3 biotech developing T Cell therapies for cancer and other diseases, filed on Friday with the SEC to raise up to $100 million in an initial public offering.

The Abingdon, United Kingdom-based company was founded in 2007 and booked $39 million in milestones for the 12 months ended September 30, 2020. It plans to list on the Nasdaq under the symbol IMCR. Immunocore Holdings filed confidentially on November 17, 2020. Goldman Sachs, J.P. Morgan and Jefferies are the joint bookrunners on the deal. No pricing terms were disclosed.

Relevant Profile: IMCR

https://www.renaissancecapital.com/IPO-Center/News/75238/Cancer-biotech-Immunocore-files-for-a-$100-million-US-IPO