NIH calls for greater inclusion of pregnant and lactating people in COVID-19 vaccine research

Longstanding obstacles to include pregnant and lactating people in clinical research have led to this population now deciding whether or not to receive a SARS-CoV-2 vaccine without the benefit of scientific evidence, writes Diana W. Bianchi, M.D., director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health, and colleagues. Their viewpoint article appears online in JAMA(link is external).

The manufacturers of currently available vaccines excluded pregnant and lactating people from the clinical trials needed to obtain Emergency Use Authorizations from the U.S. Food and Drug Administration. Now that the vaccines have been distributed, the U.S. Centers for Disease Control and Prevention and the FDA will obtain information from those who receive them on their potential impact during pregnancy, as well as information on infant outcomes. While these data will prove useful, pregnant people and their clinicians must make real-time decisions now about the vaccine based on little or no scientific evidence that applies specifically to them.

In 2016, the 21^st Century Cures Act established the Task Force on Research Specific to Pregnant Women and Lactating Women, representing multiple federal agencies, academia, industry and non-profit organizations. The Task Force developed recommendations on how to safely and ethically include pregnant and lactating people in clinical research. These recommendations must now be implemented to ensure pregnant people receive the same evidence that non-pregnant adults receive to make informed decisions about their medical care.

Recent findings from a National Institutes of Health study suggest COVID-19 during pregnancy can carry a higher risk for complications. Pregnant people need to be protected through research rather than from research, the authors contend.

Experimental COVID-19 Vaccine Protects Upper and Lower Airways in Nonhuman Primates

NIAID-Led Study of mRNA Vaccine Supports Advance to Phase 3 Human Trials

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Two doses of an experimental vaccine to prevent coronavirus disease 2019 (COVID-19)  induced robust immune responses and rapidly controlled the coronavirus in the upper and lower airways of rhesus macaques exposed to SARS-CoV-2, report scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.  SARS-CoV-2 is the virus that causes COVID-19.

 

Colorized scanning electron micrograph of a cell (blue) heavily infected with SARS-CoV-2 virus particles (red), isolated from a patient sample. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.
Credit: NIAID

The candidate vaccine, mRNA-1273, was co-developed by scientists at the NIAID Vaccine Research Center and at Moderna, Inc., Cambridge, Massachusetts. The animal study results published online today in the New England Journal of Medicine complement recently reported interim results from an NIAID-sponsored Phase 1 clinical trial of mRNA-1273. The candidate mRNA-1273 vaccine is manufactured by Moderna.

In this study, three groups of eight rhesus macaques received two injections of 10 or 100 micrograms (µg) of mRNA-1273 or a placebo. Injections were spaced 28 days apart. Vaccinated macaques produced high levels of neutralizing antibodies directed at the surface spike protein used by SARS-CoV-2 to attach to and enter cells. Notably, say the investigators, animals receiving the 10-µg or 100-µg dose vaccine candidate produced neutralizing antibodies in the blood at levels well above those found in people who recovered from COVID-19. 

The experimental vaccine also induced Th1 T-cell responses but not Th2 responses. Induction of Th2 responses has been associated with a phenomenon called vaccine-associated enhancement of respiratory disease (VAERD). Vaccine-induced Th1 responses have not been associated with VAERD for other respiratory diseases. In addition, the experimental vaccine induced T follicular helper T-cell responses that may have contributed to the robust antibody response.

Four weeks after the second injection, all the macaques were exposed to SARS-CoV-2 via both the nose and the lungs. Remarkably, after two days, no replicating virus was detectable in the lungs of seven out of eight of the macaques in both vaccinated groups, while all eight placebo-injected animals continued to have replicating virus in the lung. Moreover, none of the eight macaques vaccinated with 100 µg of mRNA-1273 had detectable virus in their noses two days after virus exposure. This is the first time an experimental COVID-19 vaccine tested in nonhuman primates has been shown to produce such rapid viral control in the upper airway, the investigators note. A COVID-19 vaccine that reduces viral replication in the lungs would limit disease in the individual, while reducing shedding in the upper airway would potentially lessen transmission of SARS-CoV-2 and consequently reduce the spread of disease, they add.  

WHO releases first guideline on digital health interventions

WHO on Wednesday released new recommendations on 10 ways that countries can use digital health technology, accessible via mobile phones, tablets and computers, to improve people’s health and essential services.

“Harnessing the power of digital technologies is essential for achieving universal health coverage,” says WHO Director-General Dr Tedros Adhanom Ghebreyesus. “Ultimately, digital technologies are not ends in themselves; they are vital tools to promote health, keep the world safe, and serve the vulnerable.”

Over the past two years, WHO systematically reviewed evidence on digital technologies and consulted with experts from around the world to produce recommendations on some key ways such tools may be used for maximum impact on health systems and people’s health.

One digital intervention already having positive effects in some areas is sending reminders to pregnant women to attend antenatal care appointments and having children return for vaccinations. Other digital approaches reviewed include decision-support tools to guide health workers as they provide care; and enabling individuals and health workers to communicate and consult on health issues from across different locations.

“The use of digital technologies offers new opportunities to improve people’s health,” says Dr Soumya Swaminathan, Chief Scientist at WHO. “But the evidence also highlights challenges in the impact of some interventions.”

She adds: “If digital technologies are to be sustained and integrated into health systems, they must be able to demonstrate long-term improvements over the traditional ways of delivering health services.”

For example, the guideline points to the potential to improve stock management. Digital technologies enable health workers to communicate more efficiently on the status of commodity stocks and gaps. However, notification alone is not enough to improve commodity management; health systems also must respond and take action in a timely manner for replenishing needed commodities. 

“Digital interventions, depend heavily on the context and ensuring appropriate design,” warns Dr Garrett Mehl, WHO scientist in digital innovations and research. “This includes structural issues in the settings where they are being used, available infrastructure, the health needs they are trying to address, and the ease of use of the technology itself.”

The guideline demonstrates that health systems need to respond to the increased visibility and availability of information. People also must be assured that their own data is safe and that they are not being put at risk because they have accessed information on sensitive health topics, such as sexual and reproductive health issues.

Health workers need adequate training to boost their motivation to transition to this new way of working and need to use the technology easily. The guideline stresses the importance of providing supportive environments for training, dealing with unstable infrastructure, as well as policies to protect privacy of individuals, and governance and coordination to ensure these tools are not fragmented across the health system.

The guideline encourages policy-makers and implementers to review and adapt to these conditions if they want digital tools to drive tangible changes and provides guidance on taking privacy considerations on access to patient data.

“Digital health is not a silver bullet,” says Bernardo Mariano, WHO’s Chief Information Officer. “WHO is working to make sure it’s used as effectively as possible. This means ensuring that it adds value to the health workers and individuals using these technologies, takes into account the infrastructural limitations, and that there is proper coordination.”

The guideline also makes recommendations about telemedicine, which allows people living in remote locations to obtain health services by using mobile phones, web portals, or other digital tools. WHO points out that this is a valuable complement to face-to-face-interactions, but it cannot replace them entirely. It is also important that consultations are conducted by qualified health workers and that the privacy of individuals’ health information is maintained.

The guideline emphasizes the importance of reaching vulnerable populations, and ensuring that digital health does not endanger them in any way.

Measles cases spike globally due to gaps in vaccination coverage

Reported measles cases spiked in 2017, as multiple countries experienced severe and protracted outbreaks of the disease. This is according to a new report published today by leading health organizations. 

Because of gaps in vaccination coverage, measles outbreaks occurred in all regions, while there were an estimated 110 000 deaths related to the disease. 

Using updated disease modelling data, the report provides the most comprehensive estimates of measles trends over the last 17 years. It shows that since 2000, over 21 million lives have been saved through measles immunizations. However, reported cases increased by more than 30 percent worldwide from 2016. 

The Americas, the Eastern Mediterranean Region, and Europe experienced the greatest upsurges in cases in 2017, with the Western Pacific the only World Health Organization (WHO) region where measles incidence fell.

“The resurgence of measles is of serious concern, with extended outbreaks occurring across regions, and particularly in countries that had achieved, or were close to achieving measles elimination,” said Dr Soumya Swaminathan, Deputy Director General for Programmes at WHO. “Without urgent efforts to increase vaccination coverage and identify populations with unacceptable levels of under-, or unimmunized children, we risk losing decades of progress in protecting children and communities against this devastating, but entirely preventable disease.”

Measles is a serious and highly contagious disease. It can cause debilitating or fatal complications, including encephalitis (an infection that leads to swelling of the brain), severe diarrhoea and dehydration, pneumonia, ear infections and permanent vision loss. Babies and young children with malnutrition and weak immune systems are particularly vulnerable to complications and death.

The disease is preventable through two doses of a safe and effective vaccine. For several years, however, global coverage with the first dose of measles vaccine has stalled at 85 percent. This is far short of the 95 percent needed to prevent outbreaks, and leaves many people, in many communities, susceptible to the disease. Second dose coverage stands at 67 percent.

“The increase in measles cases is deeply concerning, but not surprising,” said Dr Seth Berkley, CEO of Gavi, the Vaccine Alliance. “Complacency about the disease and the spread of falsehoods about the vaccine in Europe, a collapsing health system in Venezuela and pockets of fragility and low immunization coverage in Africa are combining to bring about a global resurgence of measles after years of progress. Existing strategies need to change: more effort needs to go into increasing routine immunization coverage and strengthening health systems. Otherwise we will continue chasing one outbreak after another.”

Responding to the recent outbreaks, health agencies are calling for sustained investment in immunization systems, alongside efforts to strengthen routine vaccination services. These efforts must focus especially on reaching the poorest, most marginalized communities, including people affected by conflict and displacement. 

The agencies also call for actions to build broad-based public support for immunizations, while tackling misinformation and hesitancy around vaccines where these exist.

“Sustained investments are needed to strengthen immunization service delivery and to use every opportunity for delivering vaccines to those who need them,” said Dr Robert Linkins, Branch Chief of Accelerated Disease Control and Vaccine Preventable Disease Surveillance at the U.S. Centers for Disease Control and Prevention (CDC) and Measles & Rubella Initiative Management Team Chair. 

The Measles and Rubella Initiative is a partnership formed in 2001 of the American Red Cross, CDC, the United Nations Foundation, UNICEF, and WHO.