Editor: Alyson Browett, MPH
NOVAVAX VACCINE The US FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) is meeting today to discuss and vote on the question of whether the benefits of Novavax’s 2-dose SARS-CoV-2 vaccine outweigh the risks of use among adults. The Novavax vaccine uses decades-old technology, and a vaccine using more traditional technology could help fill gaps in vaccination coverage among those who are hesitant to be vaccinated with shots using newer mRNA technology. In clinical trials, the vaccine demonstrated 90.4% efficacy in preventing mild, moderate, or severe infections with older variants, and 100% efficacy in preventing moderate or severe infection. However, it is unclear how effective the vaccine is against currently circulating Omicron subvariants. There also are concerns over the risk of the heart conditions myocarditis and pericarditis associated with the vaccine, particularly among young men, outlined in a briefing document for the meeting. These rare occurrences of heart inflammation also are associated with the Pfizer-BioNTech and Moderna mRNA vaccines. Notably, there is not enough data to evaluate the Novavax vaccine for use among pregnant women, children, or immunocompromised individuals.
If VRBPAC recommends the vaccine and the FDA grants emergency use authorization, after also evaluating information about the company’s manufacturing processes, the vaccine will be the fourth authorized for use in the US and could be available later this summer. The Novavax vaccine, one of 6 candidates supported by Operation Warp Speed, is authorized for use among adults in dozens of countries, as well as by the WHO and European Union.
BOOSTER EFFECTIVENESS DURING OMICRON Researchers continue to examine the effectiveness of SARS-CoV-2 vaccines booster doses in preventing infection during Omicron predominance. A research letter published on June 2 in JAMA examines the association between booster doses and Omicron infections among US National Basketball Association (NBA) players and staff between December 1, 2021, and January 15, 2022. A full vaccine regimen and a booster dose was required for staff members, but vaccination was optional for players. During the study period, the proportion of participants who were fully vaccinated but not boosted dropped from 26% to 8%, while the proportion of participants who received a booster rose from 49% to 85%. There were 608 SARS-CoV-2 infections among the boosted population and 127 infections among the unboosted population. While it appears that more cases occurred among vaccinated individuals, it is important to remember that the total size of the 2 populations varied widely. As a result, the whole number must be standardized to accurately reflect booster effectiveness. Overall, the study found that boosted participants were significantly less likely to develop SARS-CoV-2 infection or symptoms of COVID-19.
Another study published in The Lancet Infectious Diseases examined the connection between booster doses and Omicron infection in Spain. The study utilized data from 3 national registries, matching individuals who had completed their primary vaccination series at least 3 months earlier with those who had not, and who were aged 40 years or older and had not previously tested positive for SARS-CoV-2. Between January 3 and February 6, 2022, the researchers looked for laboratory-confirmed infections among the study population, finding the average estimated effectiveness for boosters protecting against Omicron infection for 1 month after administration was 51%. Notably, booster effectiveness was higher when a longer time passed between the initial primary vaccine regimen and the booster dose. Effectiveness also varied slightly depending on which vaccine was used for the booster. Overall, both studies indicate that booster doses of SARS-CoV-2 vaccines remain an effective means of protection, even if only for a short period of time following vaccination.
NEXT-GENERATION VACCINE DEVELOPMENT Health experts in the US are discussing the next generation of SARS-CoV-2 vaccines. While individuals who are fully vaccinated and boosted have a lower overall risk of COVID-19-associated hospitalization and death than people who are not up-to-date on their vaccinations, even boosted populations can acquire and transmit SARS-CoV-2 due to waning immunity and the ability of newer Omicron subvariants to evade both natural and vaccine-induced immunity. As a result, the US FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) is scheduled to meet on June 28 to discuss whether and how the SARS-CoV-2 strain composition of vaccines should be modified. Pfizer-BioNTech and Moderna are conducting clinical trials of modified versions of their vaccines that target multiple variants, including more recent Omicron subvariants, and 2 additional novel SARS-CoV-2 vaccine designs are in clinical trials, including a plant-based vaccine and a receptor binding domain (RBD)-dimer-based vaccine. Additionally, different delivery methods, such as inhaled nasal administration, could produce better mucosal immunity and potentially reduce breakthrough infections.
As the next generation of SARS-CoV-2 vaccines are being developed, health officials are speculating about whether booster doses will be needed annually, similar to a flu shot. The aspiration is a pancoronavirus that protects against all variants and sublineages, including possibly yet-to-emerge versions. While some experts believe the science is available to develop a pancoronavirus vaccine, the sense of urgency and the funding for such an effort are not. The US Congress remains deadlocked over negotiations for additional COVID-19 funding that would help progress research on future SARS-CoV-2 vaccines.
US VACCINE WASTE According to data from the US CDC, more than 82 million doses (11%) of distributed SARS-CoV-2 vaccines in the US were wasted between December 2020 and May 2022. This demonstrates an upward trend, as roughly 65 million doses were estimated to be wasted as of February 2022, when the figures were last reported. Over a quarter of doses thrown away were distributed by CVS (11.8 million doses) and Walgreens (8.3 million doses), the 2 largest US retail pharmacy chains. Other pharmacies and health centers, including Rite Aid, Costco, and DaVita, wasted fewer overall doses but a higher share of their received doses than CVS and Walgreens. Demand for the vaccines has plateaued, and in some parts of the country demand has dropped. Less than half of fully vaccinated US residents have received a booster shot (47%) as of June 6.
Packaging is a large contributing factor to vaccine wastage. The SARS-CoV-2 vaccines are packaged in multidose vials, and if a vial is not quickly used after opening, it has to be discarded due to their short shelf life under emergency authorizations. Concerns around vaccine wastage due to packaging are not unique to the US. Prior to the COVID-19 pandemic, the WHO cautioned that large vaccination campaigns using multidose vials will experience significant rates of vaccine wastage. The CDC is working with vaccine manufacturers to produce single-dose vials to help reduce waste. Additionally, Pfizer is making adjustments to extend shelf-life, improve handling and storage requirements, and minimize waste.
OMICRON SUBVARIANT IMPACTS Sublineages of the Omicron variant of concern continue to edge out previously dominant variants. Prevalence of the latest subvariant, BA.2.12.1, nearly tripled in the US between mid-April and late-May, and it appears the newer BA.4 and BA.5 sublineages are gaining ground among the nation’s population. However, the US CDC is aggregating genomic data with B.1.1.529, making it difficult to parse out exactly what proportion of cases are due to these newest subvariants. While much of the population has some immunity from either previous infection or vaccination, with or without 1 or 2 booster doses, reinfection remains a real risk as immunity fades over time or newer, potentially more transmissible or virulent, variants emerge. BA.4/5 appear to cause little severe disease but are highly transmissible and capable of immune escape, so we likely can expect another wave of infection due to these subvariants. Notably, BA.4/5 appear to be responsive to boosters, albeit with waning protection, as well as monoclonal antibodies and antivirals. However, unvaccinated individuals, even those with some immunity from infection with previous strains, are most at risk of severe COVID-19 outcomes.
A new report, which is not yet peer-reviewed, estimates the US death toll of each variant. According to the researchers from Yale University and Public Citizen, nearly half of COVID-19 deaths (46%) have occurred after the ancestral strain of SARS-CoV-2 was replaced by variants. The research dispels the myth that Omicron causes less severe disease than previous variants. This year, more deaths have been among older adults, especially those in long-term care facilities. The research highlights the importance of continuing vaccination and other public health strategies as long as the virus is circulating and underlines the need for additional surveillance to detect the emergence of new variants. A partnership among the US CDC, Ginkgo Bioworks Inc., and the airport-based massage and nail salon XpresSpa is hoping to fill some surveillance gaps, launching a testing service for international travelers that already has found both positive cases and new SARS-CoV-2 mutations. This type of partnership, if continued and expanded, could help to monitor for other biological threats into the future.
PAXLOVID EFFECTIVENESS The US FDA authorized the COVID-19 antiviral treatment Paxlovid in December 2021 for early COVID-19 treatment among anyone aged 12 and older who are at high risk for progression to severe COVID-19 based on data collected from its use among unvaccinated individuals during the Delta variant surge of 2021. An accepted manuscript by researchers in Israel published last week in Clinical Infectious Diseases evaluates the effectiveness of Paxlovid in a real-world setting among vaccinated and unvaccinated adults during Omicron variant predominance. According to the study, treatment with Paxlovid reduced the risk of severe COVID-19 or death by about half (46%) regardless of vaccination status, while up-to-date vaccination reduced the risk 80%. Notably, Paxlovid was more effective in older patients, immunocompromised patients, and those with underlying neurological or cardiovascular disease, and no interaction was observed between Paxlovid therapy and vaccination status.
Another preprint study posted to Research Square, also conducted by Israeli researchers, suggests Paxlovid is most effective among older adults (>=65 years), reducing the risk of COVID-19 hospitalization by 67% and COVID-19 mortality by 81%. However, patients aged 40-64 years, regardless of prior immunity, saw no significant benefit from Paxlovid treatment in reducing the risk of severe COVID-19 outcomes. Some people are experiencing what is being called “Paxlovid rebound” or “COVID rebound”—a resurgence in viral load and symptoms days after finishing the 5-day course of medicine—although data on how many patients experience the rebound or their demographics are not available at this time. Pfizer, which makes the treatment, said it plans to spend US$120 million to boost its production to make 120 million courses this year.
The White House continues to expand its test-to-treat initiative, doubling the number of sites where Paxlovid is available nationally over the past 2 months. Additionally, the number of US prescriptions filled each week has increased nearly 7-fold over the past 2 months, according to a White House fact sheet published 2 weeks ago. Importantly, both studies from Israel, which showed the greatest benefit among older patients, call into question the widespread use of Paxlovid in the US. More than 1 million courses of the drug have been administered in the US, but it remains unclear who is taking it.
VACCINE MISINFORMATION DURING PREGNANCY Pregnancy-related misinformation about SARS-CoV-2 vaccines is common and persistent, leading about 1 in 5 US adults (18%) and about 3 in 10 women who are pregnant or planning to become pregnant (29%) to believe in at least 1 of 3 false statements about vaccines and pregnancy, according to the latest findings of the Kaiser Family Foundation’s COVID-19 Vaccine Monitor. Larger proportions of those surveyed said they believe or are unsure of at least 1 of 3 false statements about pregnancy and SARS-CoV-2 vaccines, including segments of the population that generally believe the vaccines are safe for adults. The survey, conducted in May, included responses from more than 1,500 US adults, including 900 women, who evaluated 3 false statements on vaccines and pregnancy, breastfeeding, and infertility. About 1 in 7 adults (14%) and almost 1 in 4 women who are pregnant or planning to become pregnant (24%) incorrectly believe pregnant women should not be vaccinated against COVID-19, according to the survey.
Pregnant people are at an increased risk of severe COVID-19 outcomes, including death, and health experts recommend that pregnant people and those looking to become pregnant remain up to date on their vaccinations. Notably, vaccination of pregnant people likely has benefits to newborns, as well. Research out of Norway, published in JAMA Internal Medicine, suggests that infants born to women who had received a second or third vaccine dose during pregnancy were 33% less likely to test positive for SARS-CoV-2 infection at age 4 months than infants born to unvaccinated women. The difference between infants born to vaccinated versus unvaccinated women was more pronounced during Delta predominance, with those born to vaccinated women 71% less likely to test positive in the 4 months following birth. About 30% of pregnant people in the US remain unvaccinated.
COVID-19 DEATHS In discussions regarding how to best articulate the end of the COVID-19 pandemic emergency phase, officials in the administration of US President Joe Biden considered using a specific threshold of daily COVID-19 deaths but decided not to use that number as a formal metric. The exercise was meant more as a thought experiment, with the continuing goal to bring down the number of new infections and deaths. An average of 247 people are dying of COVID-19 each day as of June 5. At no point since the beginning of the pandemic have fewer than 200 people died of COVID-19 per day in the US for a sustained time period.