Editor: Alyson Browett, MPH

Contributors: Clint Haines, MS; Noelle Huhn, MSPH; Natasha Kaushal, MSPH; Amanda Kobokovich, MPH; Christina Potter, MSPH; Matthew Shearer, MPH; Marc Trotochaud, MSPH; and, Rachel A. Vahey, MHS.

CALL FOR PAPERS In 2023, Health Security will devote a supplement to Global Catastrophic Biological Risks (GCBRs). We encourage submissions of original research articles, case studies, and commentaries that discuss lessons learned from the COVID-19 pandemic response and/or key policy and technology advances that could prevent or better prepare for a future, potentially more severe, globally catastrophic infectious disease pandemic. The deadline is October 3, 2022. Click here more information.

NOTICE The COVID-19 Situation Report will not be published on July 5 or July 7. The report will resume publication the following week on July 12.

EPI UPDATE The WHO COVID-19 Dashboard reports 543 million cumulative cases and 6.33 million deaths worldwide as of June 29. The global weekly incidence increased 21.32% from the previous week. Global weekly mortality increased as well, up 7.43% from the previous week. At the regional level, Europe (+40%), the Americas (+15%), Southeast Asia (+32%), and the Eastern Mediterranean (+47%) experienced increases, while the Western Pacific (-3%) and Africa (-34%) had decreasing trends. The number of new weekly deaths increased in the Eastern Mediterranean (+22%), Southeast Asia (+15%), and the Americas (+11%) and decreased in the Western Pacific (-6%), Europe (-5%) and Africa (-1%).

The US CDC is reporting 87.2 million cumulative cases of COVID-19 and 1,012,166 deaths. The average daily incidence has plateaued over the past several weeks, holding relatively steady at approximately 100-110,000 new cases per day. The current 7-day average is 108,505 new cases per day. The average daily mortality has held relatively steady at approximately 250-300 deaths per day since late May* However, the 7-day average appears to be rising and currently is 321 deaths per day.

Both new hospital admissions (+13% over the past week) and current hospitalizations (+5%) continue to increase. Considering the plateau in daily incidence, it is possible that hospitalizations could also remain elevated, rather than peaking and then declining.

Community transmission in the US is now being driven by the Omicron BA.5 (36.6%) and BA.4 (15.7%) sublineages, which together are now more prevalent than the BA.2.12.1 sublineage (42%). Along with BA.2 (5.7%), these 4 sublineages of the Omicron variant represent all new SARS-CoV-2 infections in the US.

OMICRON BA.4/BA.5 SARS-CoV-2 Omicron subvariants BA.4 and BA.5 have overtaken BA.2.12.1 as the dominant strains in the US. While BA.2.12.1 still makes up approximately 42% of new cases as of June 25, BA.4 accounts for 15.7% and BA.5 accounts for 36.6%, for a combined total of 52.3%. BA.4 and BA.5 were first detected in South Africa in November 2021, and they are now fueling a worldwide increase in cases. Additionally, hospitalizations are on the rise in Israel, Portugal, South Africa, the UK, and the US. The increases in case and hospitalization numbers are likely due to the fact that BA.4 and BA.5 contain mutations that are believed to aid in immune evasion. This means that prior infection with an earlier Omicron strain, such as BA.1 from winter 2022, might not be enough to protect against disease. BA.4 and BA.5 also are capable of escaping some immunity from vaccines, but vaccinated individuals still tend to fare better than those relying on natural immunity alone. It is increasingly likely that more individuals will start experiencing reinfections. There are concerns that multiple reinfections could put individuals at a higher risk for health problems, but research on the matter is ongoing. 

In a June 29 briefing, WHO Director-General Dr. Tedros Adhanom Ghebreyesus noted that BA.4 and BA.5 are responsible for an approximately 20% increase in the number of COVID-19 cases worldwide. COVID-19 cases are on the rise in 110 countries and deaths are increasing in half of the 6 regions monitored by the WHO. Dr. Tedros also spoke out against complacency in the face of the pandemic, stressing that the pandemic is changing and not yet over. He urged the international community to quickly work toward achieving 100% vaccination rates for healthcare workers and individuals over age 60 years. Dr. Tedros also re-emphasized the need for a pan-coronavirus vaccine that can stand up to the rapid evolutionary rate of SARS-CoV-2. Notably, BioNTech announced this week that the company and its partner Pfizer will begin human trials of a pan-coronavirus vaccine in the second half of the year. 

VACCINE UPDATES FOR OMICRON The US FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) on June 28 voted 19-2 to recommend the agency take steps to authorize updated COVID-19 booster shots targeting some form of the SARS-CoV-2 Omicron variant that has been dominant since the beginning of this year. A confluence of factors makes the US population more susceptible to a winter COVID-19 surge, including waning immunity, the possible emergence of a new variant, and colder weather that pushes more people indoors. Current vaccines and boosters are based on the spike protein structure and characteristics of only the original SARS-CoV-2 virus, so introducing individuals to an Omicron spike protein should broaden the body’s immune response against additional versions of the virus, whether currently circulating or a future but similar variant. Many committee members expressed dismay over the limited amount of data on updated vaccine formulations—including if or how well they might provide additional protection—and unknowns about which variants will be circulating this fall.

In an announcement released today, the FDA said that based on the committee’s discussions, it has advised manufacturers seeking to update their COVID-19 vaccines to develop modified versions that add spike protein components of the Omicron BA.4/BA.4 subvariants to current vaccine formulations to create a 2-component, or bivalent, booster vaccine. The decision paves the way for vaccine companies to start manufacturing Omicron-containing doses to potentially be ready for use beginning in early to mid-fall. The FDA did not recommend a change to the primary vaccination formulations. 

Introducing another booster this year may come with its own suite of challenges in terms of communication, including possibly moving away from the term booster to something like “another annual shot.” A significant proportion of individuals in the US who are eligible to receive third or fourth shots have yet to do so, leaving them more vulnerable as BA.4 and BA.5 become predominant and highlighting the need for a comprehensive communication strategy about who should get additional shots, when, and why. The administration of US President Joe Biden on June 29 announced an agreement to purchase 105 million doses of the Pfizer-BioNTech COVID-19 vaccine for US$3.2 billion for a fall vaccination campaign, with options for an additional 195 million doses. Pfizer-BioNTech will provide its new formulation based on FDA recommendations. Both Pfizer-BioNTech and Moderna are working on vaccine booster reformulations.

US MATERNAL MORTALITY A new study examining maternal mortality rates in the US before and during the COVID-19 pandemic was published June 28 in the peer-reviewed journal JAMA Network Open. The study compared pre-pandemic and pandemic maternal mortality using de-identified records from the National Center for Health Statistics. Deaths occurring in 2018, 2019, or January-March 2020 were classified as pre-pandemic. Deaths occurring from April-December 2020 were classified as during the pandemic. The study found that maternal mortality rose from 18.8 per 100,000 live births to 25.1 per 100,000 live births. This represents an increase of 33%, higher than the 22% increase in mortality expected as a result of the pandemic. Late maternal mortality increased 41%. 

The largest increases in maternal mortality were seen in Hispanic populations, at 74.2%, and non-Hispanic Black populations, at 40.2%, compared to an increase of 17.2% in non-Hispanic White populations. The largest increases in maternal mortality were seen for underlying cause-of-death codes related to indirect causes of death such as other viral diseases (2,374.7%), diseases of the respiratory system (117.7%), and diseases of the circulatory system (72.1%). Maternal mortality increases associated with direct causes of death were largely due to diabetes (95.9%), hypertension disorders (39%), and other pregnancy-related conditions (48%). The authors call for future studies that examine ethnic and racial disparities along with specific causes of COVID-19-related maternal mortality. They also expressed hope that improvements due to the rollout of vaccines could be realized in future analyses. 

The new study further confirms a trend seen before the pandemic, when maternal mortality rates were twice as high in the US as in many other high-income countries. More resources are needed to protect pregnant populations from the dangers associated with COVID-19, but pre-existing issues that lead to high maternal mortality must also be addressed to protect this often overlooked high-risk population in the US. 

MONOCLONAL ANTIBODY THERAPIES The US government is expected to use up its supplies of Eli Lilly’s monoclonal antibody therapy for COVID-19 in late August because its pandemic funding is running out. Lilly said it agreed to supply the US with an additional 150,000 doses of bebtelovimab for about US$275 million in order to meet demand through the end of August. The agreement includes an option for an additional 350,000 doses that must be applied no later than September 14. Currently, the federal government is distributing about 30,000 doses per week. The antibody received US FDA emergency use authorization earlier this year for use among non-hospitalized patients with mild-to-moderate COVID-19 who are at high risk of disease progression, and the drug has shown effectiveness against the Omicron variant. If the federal government is unable to procure more doses than currently agreed upon, Lilly will need to sell the treatment directly to hospitals and states, a move that would represent a first test of shifting a COVID-19-related drug to the commercial market.

The US FDA and the Assistant Secretary for Preparedness and Response (ASPR) authorized a shelf-life extension for another monoclonal antibody therapy, Evusheld (tixagevimab co-packaged with cilgavimab) made by AstraZeneca. The shelf life of certain lots of the refrigerated treatment can be extended from 18 months to 24 months. Evusheld is authorized for pre-exposure prophylaxis of COVID-19 in certain adults and pediatric individuals. Several experts are hoping for more funding and research into antibody treatments for COVID-19 and other ailments, with some noting that antibodies can have more long-lasting impacts than vaccines, especially among people with immunodeficiencies, and could serve as a key solution during the next pandemic. 

DIGITAL SOLUTIONS FOR INFODEMIC During the COVID-19 pandemic, the public has been faced with an overabundance of information, including false or misleading content, in both online and offline environments. To address the online information epidemic, the WHO Regional Office for Europe published a policy brief on how digital solutions can be used to address this so-called “infodemic” to help improve the public health response to COVID-19 and future health emergencies. The brief outlines what WHO is doing to address the infodemic in Europe and globally and highlights 6 specific policy considerations for policymakers and other key stakeholders to help improve infodemic management, including reinforcing multistakeholder networks for infodemic management; strengthening overall risk communication and community engagement; implementing continuous monitoring of harmful and false online content; improving digital literacy approaches and organizing infodemic management trainings; advocating for infodemic management through communication campaigns; and ensuring safe online platforms, which protect people from harmful content.

RESEARCH ROUNDUP The research roundup provides quick synopses of COVID-19-related research.

From Emerging Infectious Diseases, a case report from Thailand of a veterinarian who was diagnosed with COVID-19 after treating and being sneezed on by a domestic cat owned by a person infected with SARS-CoV-2 at the time. Genetic analysis supports the hypothesis that viral transmission occurred from the owner to the cat and then from the cat to the veterinarian. Notably, the veterinarian was wearing an N95 during the cat’s examination, leading the researchers to postulate her eyes were left vulnerable to infection when the cat sneezed in her face, highlighting the importance of face shields or goggles, in addition to masks, to prevent transmission.

From JAMA Internal Medicine, a study suggesting that patients of African ancestry with sickle cell trait (SCT) and associated history of one of several kidney conditions were at increased risk of mortality and acute kidney failure following COVID-19. The results strongly support advising that patients with SCT be regarded as at high-risk of COVID-19.

From The Journal of Infectious Diseases, a cohort study evaluating the risk of SARS-CoV-2 infection and severe COVID-19 disease in persons with Down syndrome (DS) and matched controls prior to available vaccination. Though the risk of infection among individuals with DS was 32% lower than their matched counterparts (aHR 0.68, 95% CI: 0.56-0.83), the rate of severe COVID-19 disease was 6-fold higher (aHR 6.14, 95% CI: 1.87-20.16). The results support better infection monitoring, early treatment, and vaccination for individuals with DS.

From the New England Journal of Medicine, a cohort study of US children aged 5-11 who were vaccinated on or after November 23, 2021, compared with matched controls who were unvaccinated to estimate the effectiveness of the Pfizer-BioNTech vaccine at the start of the Omicron surge. The estimated vaccine effectiveness against symptomatic COVID-19 was 18% (95% CI: -2 to 34) at 14 to 27 days after the first dose and 48% (95% CI: 29 to 63) at 7 to 21 days after the second dose, showing moderate protection as Omicron was becoming dominant. 

From Pediatrics, a multicenter prospective observational cohort study conducted in 25 US pediatric hospitals that followed COVID-19 patients under age 21 who were hospitalized between May 2020 and May 2021 for COVID-19 or multisystem inflammatory syndrome in children (MIS-C) for 2-4 months after admission. The researchers found that more than 1 in 4 children with COVID-19 or MIS-C experienced persistent symptoms or activity impairment for at least 2 months. Those patients with MIS-C who have respiratory problems or obesity had a higher risk of prolonged recovery.

From Scientific Reports, a mathematical modeling study examining how human movement—from home to other locations such as school, work, and elsewhere—social distancing behavior, and other restrictive measures such as quarantine affect COVID-19 dynamics within a population. The study’s model showed that SARS-CoV-2 transmission is most attributable to the home location, including gatherings of relatives and close friends. Therefore, limiting encounters or travel to other locations is only effective if the same social distancing measures are also effectively implemented in the home setting.