EPI UPDATE The WHO COVID-19 Dashboard reports 623 million cumulative cases and 6.55 million deaths worldwide as of October 19. Global weekly incidence again remained steady at slightly more than 3 million cases for the sixth consecutive week, decreasing only 0.87% compared to the previous week. Weekly incidence in Europe remained relatively steady over the previous week, falling 3% after steady increases for the previous 4 weeks. Weekly incidence increased 11% in the Western Pacific, while all other regions reported decreasing trends. Global weekly mortality continued to decrease for the ninth consecutive week, down 15% from the previous week.
The US CDC is reporting 96.8 million cumulative cases of COVID-19 and 1.06 million deaths. Daily incidence continues to decline, down to 37,052 new cases per day, the lowest average since mid-April. Average daily mortality also continues to decline, down to 323 deaths per day on October 18.**
**Changes in state-level reporting may affect the accuracy of recently reported data, particularly over weekends. In an effort to reflect the longer-term trends, the numbers reported here may not correspond to the most recent dates.
Both new hospital admissions and current hospitalizations continue to exhibit downward trends, with decreases of 1.8% and 3.3%, respectively, over the past week. Both trends peaked around the end of July, although the decreasing trend appears to be leveling.
The BA.5 sublineage continues to be the dominant strain in the US, accounting for 67.9% of sequenced specimens; however, its estimated prevalence has decreased for 8 consecutive weeks. Notably, the BA.4.6 sublineage (12.2%) appears to be losing its growth advantage to others, including BQ.1 (5.7%), BQ.1.1 (5.7%), and BF.7 (5.3%). BA.2.75.2 (1.4%) and BA.2.75 (1.3%) also show relative growth advantage over BA.5.
IMMUNE EVASIVE OMICRON SUBVARIANTS While past surges in COVID-19 cases have been driven largely by single SARS-CoV-2 variants, experts are eyeing a collection of Omicron subvariants that could drive an anticipated wave of infections this fall and winter. In the US, BA.4.6 appeared to be gaining momentum, although BF.7, BQ.1, and BQ.1.1 are showing recent potential growth advantage. The same sublineages are also showing evidence of growth advantage over BA.5 in the United Kingdom. Additional variants, including the recombinant variant XBB, are fueling increases in cases in Southeast Asia and Europe. The US has yet to see a large surge due to these subvariants, with the number of new cases continuing to drop. But public health experts warn data on new cases is unreliable—many are turning to wastewater surveillance to help predict where and when surges may occur—and most expect the downward trend to reverse over the next few weeks. The collection of variants, sometimes referred to as “scrabble variants” or “subvariant soup,” accounts for nearly 1 in 3 new infections reported in the US last week. Globally, detecting these variants and developing accurate assessments of the risk they pose to public health is challenging, as many countries have rolled back their surveillance efforts.
While available vaccines remain effective in preventing severe illness and death from COVID-19, there are concerns the emerging subvariants will be more immune evasive than previous variants, particularly due to mutations in the receptor binding domain that would prevent antibodies from docking and attacking the virus. AstraZeneca’s EvuSheld, the only monoclonal antibody authorized to prevent SARS-CoV-2 infection, is ineffective against BA.4.6. Other monoclonal antibodies in development already demonstrate vulnerabilities to newly emerging Omicron subvariants. With this new information, the Biden administration is searching for other potential candidates for use among immunocompromised persons.
US RESPONSE With public vigilance waning and the hopes of new pandemic funding from the US Congress fading, the COVID-19 response in the US is entering a new and uncertain phase. Omicron subvariants remain the predominant circulating lineages, many with high levels of transmissibility and immune evasion. Most places have completely dropped public health measures meant to mitigate transmission, and fewer and fewer Americans are wearing masks indoors or in crowded public spaces. With lower vaccine demand and less federal funding, vaccine manufacturers must soon decide whether and how high to price vaccines and boosters moving forward. While people with health insurance likely will continue to be able to access free or low-cost COVID-19 vaccines and therapies, those who are uninsured or underinsured potentially could lose no-cost access, a factor that would exacerbate underlying inequities. One factor influencing when COVID-19 tools will be commercialized is when the public health emergency declaration ends; however, the Biden administration last week extended the public health emergency for another 90 days, into January 2023, ahead of an expected potential winter surge. This decision aligns with a recent statement from the WHO reinforcing that COVID-19 very much remains a global emergency and calling for nations to sustain efforts to fight against its spread. Still, the US likely will end its public health emergency in 2023, when it will significantly cut back on certain components of its COVID-19 response.
Notably, efforts are underway to prevent such a situation from happening again in the future. On October 18, US President Joe Biden signed a National Security Memorandum to launch the administration’s “National Biodefense Strategy and Implementation Plan for Countering Biological Threats, Enhancing Pandemic Preparedness, and Achieving Global Health Security.” The strategy calls for US$88 billion in funding over the next 5 years to strengthen key areas of pandemic preparedness and biodefense. The strategy will also bring together key government sectors to support its implementation, including the White House, the Intelligence Community, the US Department of State, and the US HHS.
GAIN-OF-FUNCTION STUDY A laboratory at Boston University has come under criticism for its recent gain-of-function experiments on the SARS-CoV-2 virus. Gain-of-function (GOF) refers to laboratory experiments that strategically and specifically enhance the function of one or more genes to study the outcome. They can range from something as simple as overactivating an important enzyme to enhancing the pathogenicity of a virus. In the Boston University (BU) experiments, performed at the BSL-3 level, the original strain of SARS-CoV-2 was modified to contain Omicron variant spike proteins with the aim of studying why some strains of SARS-CoV-2 are more pathogenic and transmissible than others. This work was reviewed internally by the BU institutional review board (IRB) and externally by the Boston Public Health Commission but not by the US NIH or NIAID, which were partial funders. NIH is currently launching a probe to evaluate whether this experiment should have been subject to federal oversight and review before moving forward. BU maintains that the research was not directly funded by the NIH and therefore there was no wrongdoing in not alerting them before beginning the experiment. The federal government takes GOF research very seriously, especially for those manipulating pathogens with potential pandemic potential, as SARS-CoV-2 certainly is. Even before the lab-leak hypothesis of SARS-CoV-2 origins, there was a large amount of controversy surrounding how and when to allow GOF research to move forward.
However, BU refutes that this experiment even should be considered as gain-of-function and maintain that they actually made a less dangerous version of the virus. The school criticized the initial media reports of the experiment, saying they were highly sensationalized; several outlets stressed the study’s finding that the altered strain caused 80% mortality in mice with severe disease, but that proportion is in line with experiments using unaltered SARS-CoV-2. Still, the finding that the resulting strain was less pathogenic does not alter the fact that the methods used fall within the definition of GOF research. Many biosecurity experts have come forward to disagree with BU’s characterization of their research and reiterate that this was in fact GOF research. The NIH inquiry and the renewed conversation among the scientific community will hopefully spur greater understanding and consensus around the risks and benefits of GOF research, in addition to institutionalizing the use of greater safeguards when conducting research with pathogens of pandemic potential.
LIFE EXPECTANCY & PREGNANCY-RELATED MORTALITY The COVID-19 pandemic interrupted decades worth of gains in global life expectancy. According to a study published October 17 in Nature Human Behaviour examining life expectancy losses during the pandemic, those countries that had higher proportions of their populations vaccinated by October 2021 experienced smaller life expectancy deficits in winter 2021. Of the 29 countries included in the analysis, most countries in Western Europe bounced back relatively well from life expectancy losses while most countries in Eastern Europe, the United States, and Chile experienced continuing declines in their pre-pandemic life expectancy. All nations had lower life expectancy than would be expected if pre-pandemic trends had continued. According to data from the US CDC, US life expectancy fell by a total of 2.6 years between 2019 and 2021 to 76.1 years, the lowest level since 1996.
In the US, COVID-19 contributed to about 25% of the more than 2,000 maternal deaths in 2020 and 2021, according to a report published by the US Government Accountability Office. Pregnant people are more vulnerable to severe COVID-19 outcomes, the US CDC has warned. Since 2018, maternal deaths have increased nearly 80%, with COVID-19 associated with 401 of the 1,178 pregnancy-related deaths last year. Additionally, racial and ethnic disparities widened; pregnancy-related deaths among Black people climbed from 44 per 100,000 in 2019 to 68.9 per 100,000 in 2021, rose from 12.6 per 100,000 in 2019 to 27.5 last year for Hispanic individuals, and increased from 17.9 in 2019 to 26.1 in 2021 for White people. Many factors contributed to the increase in maternal deaths, including the emergence of the Delta variant, mental health, lack of access to medical care, and low vaccination rates among pregnant people, among others. Experts note that many of these deaths were preventable, highlighting the urgent need to find solutions.
US CDC VACCINES FOR CHILDREN PROGRAM The US CDC Advisory Committee on Immunization Practices (ACIP) on October 19 recommended that vaccines against COVID-19 be included in the CDC Vaccines for Children program, which provides no-cost vaccines for a variety of diseases to children and adolescents aged 18 and younger whose families cannot afford them. Children are eligible for the program if they qualify for Medicaid, or are uninsured, underinsured, or Native American. The panel of independent advisors voted unanimously to include COVID-19 vaccines in the program to ensure these children can receive the shots for free after the federal government shifts the vaccination program to the commercial market. When the Biden administration decides to end the COVID-19 public health emergency—which it extended again last week—more than 5 million children are expected to lose health insurance under federal programs.
During the meeting, the panel emphasized they were not voting on adding COVID-19 vaccines to the CDC annual vaccination schedule, although a meeting to consider doing is taking place today. While the CDC decides a recommended vaccination schedule for children based on age, US states decide which vaccines are mandatory for entry into schools. Nonetheless, the CDC had to push back on a Fox News contributor who amplified a false claim that the CDC was set to mandate COVID-19 vaccines for schoolchildren. Public health experts agree there is legitimate debate over whether school-aged children should be required to receive the vaccines but warned the erroneous claim represents another example of how quickly misinformation can spread and potentially harm children, erode trust in federal health institutions, or endanger health officials. Experts also agree more states and localities will require children be vaccinated to attend the upcoming 2023 school year.
NOVAVAX BOOSTER On October 19, the US FDA authorized Novavax’s monovalent, protein-based COVID-19 vaccine as a booster for adults. The Novavax booster targets only the original coronavirus strain, although the company is concurrently studying an Omicron-targeting vaccine, in addition to a bivalent booster. The US CDC recommended the monovalent product for use among adults aged 18 years and older who have not yet received any COVID-19 booster but who have completed a primary series vaccination with any authorized or approved vaccine at least 6 months prior. The authorization offers another option for individuals who cannot or are reluctant to receive one of the bivalent mRNA vaccine boosters, or for those who would otherwise not receive a booster.
MODERNA OMICRON BOOSTERS Moderna’s bivalent Omicron-containing booster (mRNA-1273.214), administered as a fourth vaccine dose, produced a stronger immune response to Omicron BA.1 compared to its original booster dose at 90 days, according to the company. Additionally, the updated booster elicited a significantly higher neutralizing antibody response against Omicron BA.4/BA.5 compared to the original version at 28 days, suggesting the booster can produce broad cross-neutralization against Omicron subvariants. Moderna’s BA.1 bivalent booster is central to fall and winter vaccination campaigns in the UK. The company expects to announce interim immunogenicity results of its Omicron BA.4/BA.5-targeting bivalent vaccine (mRNA-1273.222), which is authorized for use in the United States, later this year. It is unclear how well either booster will work against newly emerging Omicron sublineages—including BQ.1.1, XBB, BF.7, and BA.2.75.2—which are expected to be more immune evasive than their older relatives and expected to cause COVID-19 surges in several nations through the end of this year and into the next.
Moderna also announced this week it will work with Gavi, the Vaccine Alliance, to supply more than 100 million doses of its Omicron-adapted bivalent vaccines for purchase at its lowest-tier pricing in 2023 to the COVAX Advance Market Commitment (AMC). Under the new framework, pending orders for Moderna’s original SARS-CoV-2 vaccine will be canceled, and COVAX will instead offer the newer vaccines to low- and middle-income countries (LMICs), which can use them as they see fit. COVAX has delivered nearly 1.8 billion doses of vaccines for COVID-19 to 146 countries, overcoming a rough start to obtain vaccine doses due to hoarding by wealthier nations. Dr. Mike Ryan, executive director of the WHO Health Emergencies Programme, this week at the World Health Summit harshly criticized wealthy nations and pharmaceutical companies for failing to adequately share vaccine doses through COVAX.