EPI UPDATE The WHO COVID-19 Dashboard reports 595 million cumulative cases and 6.45 million deaths worldwide as of August 25. Global weekly incidence decreased for the second consecutive week, down 8% from the previous week. Global weekly mortality appears to have peaked as well, down 13.5% from the previous week.

Regional trends in weekly incidence and mortality also are declining. All regions, with the exception of the Western Pacific, reported decreases in weekly incidence, ranging from -13% to -23% from the previous week. Notably, the Western Pacific reported a slight increase (+1.6%), but the weekly total was still 17% lower than the most recent peak reported the week of August 1. Weekly mortality is declining in all regions except the Eastern Mediterranean and Western Pacific. The Eastern Mediterranean region does appear to be at or near a peak, so if it follows the global trends, we expect weekly mortality to begin decreasing in the next week or two. The Western Pacific region’s weekly mortality continues to increase substantially, up 7.7% over the previous week and 2.5 times the most recent low reported the week of July 11. In light of the region’s sharp peak in weekly incidence several weeks ago, we expect to observe a corresponding decline in mortality over the next week or two.*

*The WHO Dashboard notes that incidence and mortality data for the Africa Region are incomplete.

UNITED STATES

The US CDC is reporting 93.6 million cumulative cases of COVID-19 and 1,036,604 deaths. Average daily incidence continues to decline, down from the most recent high of 129,359 new cases per day on July 21 to 89,698 on August 23—the lowest average since May 12. Average daily mortality appears to have passed a peak, down from 466 deaths per day on August 12 to 390 on August 23. A lag in daily mortality of 2-4 weeks behind daily incidence is consistent with the trends we have observed over the course of the pandemic.**

**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 decline, down 3.3% and 6.6%, respectively, over the past week. Both trends peaked around the last week of July, similar to trends in daily incidence.

The BA.5 sublineage is projected to account for 88.9% of sequenced specimens in the US. While BA.5 remains the overwhelmingly dominant variant—and continues to increase in prevalence—the prevalence of the BA.4.6 sublineage is increasing as well. Over the past 2 weeks, BA.4.6 became the #2 variant nationwide, now accounting 6.3% of sequenced cases, while BA.4 fell to #3 (4.3%). It remains unclear whether BA.4.6 is capable of usurping BA.5 in the US, but its increasing prevalence could potentially indicate that it is competing well against the dominant variant. Collectively, the remaining variants account for only 0.5% of cases nationally. All variants reported here are sublineages of the Omicron variant of concern (VOC).

US BOOSTER CAMPAIGN Following recent news regarding the authorization of variant-adapted SARS-CoV-2 vaccine boosters in the UK and applications for emergency use authorization (EUA) of BA.4/BA.5 boosters in the US (both Pfizer-BioNTech and Moderna), US government officials have signaled that variant-adapted booster doses could be available for individuals aged 12 years and older by early September. The bivalent vaccines will target both the original strain of SARS-CoV-2 and both the BA.4 and BA.5 sublineages (since they share common mutations to the spike protein).

While human clinical trials have not yet been conducted, the agency’s Director of the Center for Biologics Evaluation and Research (CBER), Dr. Peter Marks, indicated that he is “extremely confident” that the trials will demonstrate the candidate boosters to be safe and efficacious. In contrast to regulatory review of previous SARS-CoV-2 vaccine candidates, the FDA is not waiting on the completion of human clinical trials. Rather, the agency will base their assessment primarily on data from animal models and previous clinical trial data on BA.1-adapted bivalent candidate vaccines, a process similar to how the FDA reviews seasonal influenza vaccines. Clinical trials for the candidate boosters in humans are expected to begin this month. Reportedly, the FDA does not intend to convene its Vaccines and Related Biological Products Advisory Committee (VRBPAC) to discuss the candidate boosters; however, the CDC’s Advisory Committee on Immunization Practices (ACIP) has tentatively scheduled a meeting for September 1-2 in anticipation of a FDA decision. 

Some experts have expressed doubt regarding the need for a BA.4/BA.5-specific booster, as it may provide little additional protection for the millions of people who have already been exposed to one of those variants. Similarly, antibodies generated to protect against BA.4/BA.5 may not provide sufficient protection against other emerging variants, such as BA.2.75. While some experts are concerned that the abbreviated regulatory review risks increasing vaccine hesitancy and mistrust among the public, others argue that it is critical to make variant-adapted boosters available quickly, to provide protection before the virus evolves further and new variants emerge.

PANDEMIC INVESTMENTS Much of the federal funding allocated to the US COVID-19 pandemic response—approximately US$3.9 trillion of US$4.5 trillion—has been spent, and the US Congress has not agreed to authorize additional funding. This leaves many wondering what is worth investing in at this point in the pandemic, when we have many tools to prevent and treat COVID-19 but also uncertainties about future SARS-CoV-2 variants. Many experts agree that funds should be directed toward developing next-generation vaccines—those that can prevent infection instead of only avoiding serious outcomes—and improving indoor air quality, which could help mitigate a host of airborne illnesses and allergens, as well as mitigate the health impacts of air pollution. Overall, they agree investments should be geared toward strategies that provide lasting benefits beyond the COVID-19 pandemic. 

The world could be entering a new age of more frequent and intense infectious disease outbreaks, with some infectious disease experts calling attention to the fact that diseases can spread quickly as international travel ramps back up. This highlights the urgent need to improve other public health efforts, including upgrading disease surveillance, data collection, and analysis; rebuilding trust in science and public health systems; taking a holistic view of health to include human-driven environmental change and animal health; closing gaps in health inequities; and boosting funding for pandemic preparedness. With some modeling showing extreme disease events similar to COVID-19 could increase 3-fold in the coming decades, the US and the world must prepare now to mitigate future epidemic, and perhaps pandemic, impacts.

PAXLOVID Several high-profile cases of COVID-19 rebound following treatment with Paxlovid—including White House Science Advisor Dr. Anthony Fauci, US President Joe Biden, and, most recently, First Lady Dr. Jill Biden—raise questions about how often such cases occur. Initial studies of the antiviral suggest that between 1% and 6% of people who take the drug experience rebound, with or without symptoms, around days 10-14 after initially testing positive. But some physicians believe rebound cases are more common, estimating between 20% and 40% of patients who take Paxlovid experience the condition, based on anecdotal evidence. The US FDA has requested that Pfizer, the drug’s manufacturer, conduct clinical trials to better understand the condition and its frequency. 

Nevertheless, Paxlovid remains highly effective at preventing serious COVID-19 among people at high-risk of disease progression, according to several studies. In a retrospective cohort study published August 24 in the New England Journal of Medicine, Israeli researchers report that the treatment reduced hospitalizations among people aged 65 years and older who were assessed as being at high risk for progression to severe disease by 73% and reduced the risk of death from complications by 81% when given shortly after infection during the Omicron surge, compared to patients who did not take the treatment. Those findings are consistent with earlier trial results. However, the researchers found Paxlovid showed no evidence of benefit among patients aged 40 to 64 years who were deemed at high risk for disease progression. Across both age groups, a lack of previous SARS-CoV-2 immunity and previous hospitalization were strongly associated with high rates of hospitalization due to COVID-19. 

In another study published the same day in The Lancet Infectious Diseases, researchers report that during the Omicron BA.2 wave in Hong Kong, early Paxlovid use was associated with a 66% lower risk of death and early use of molnupiravir—another authorized antiviral, also known as Lagevrio and made by Merck—was associated with a 52% lower risk of death among hospitalized COVID-19 patients who did not need oxygen supplementation. Additionally, patients who took antivirals had a lower risk of disease progression and significantly shorter times reaching low viral burden than those who did not receive the treatments. Taken together, the studies support the continued use of antiviral therapeutics authorized to treat COVID-19 among certain populations, including older patients and those who are hospitalized but not requiring oxygen therapy upon admission, but raise questions for the use of the treatments among the general population. In the US, Paxlovid is authorized for the treatment of mild-to-moderate COVID-19 in certain adult and pediatric patients aged 12 years or older who are at high risk of disease progression, and Lagevrio is authorized for the treatment of mild-to-moderate COVID-19 in high-risk adults aged 18 or older who are at high risk of severe COVID-19 and for whom alternative treatment options are not accessible or clinically appropriate. 

VACCINE EFFICACY AMONG YOUNG CHILDREN On August 23, Pfizer and BioNTech announced that their 3-dose primary series SARS-CoV-2 vaccine showed 73.2% efficacy among children younger than 5 years old without evidence of prior infection. The study was conducted during a time when the Omicron BA.2 subvariant was predominant. Among 794 children who were fully vaccinated, 13 were infected, compared with 21 of 351 children who received placebo doses. The vaccine was 75.8% effective among children younger than 23 months old and 71.8% effective among toddlers aged 2 to 4 years old. Sequencing of viral RNA from nasal swabs indicated that cases of COVID-19 among trial participants were primarily caused by Omicron BA.2. Given that the Omicron BA.4 and BA.5 subvariants emerged during the trial and now cause most infections among US adults, the companies indicated their intent to request US FDA emergency use authorization (EUA) of an Omicron BA.4/BA.5-adapted bivalent vaccine in children ages 6 months through 11 years. Though these results continue to illustrate that the Pfizer-BioNTech vaccine is safe, effective, and well-tolerated among children—and despite a national push to vaccinate more children—less than 5% of US children under age 5 have been vaccinated.

LONG COVID/PASC Many researchers are baffled by post-acute sequelae of SARS-CoV-2 infection (PASC) and post-COVID-19 conditions, often referred to as long COVID, a persisting condition affecting some people who have recovered from acute SARS-CoV-2 infection, for which symptoms are vaguely defined, vary in prevalence and severity, and are sometimes difficult to attribute to COVID-19. Despite centuries of evidence showing that viral infections can leave long-term, often debilitating, health complications in their wake, many suffering from long COVID and their advocates are urging more research and support to define and treat the condition. Earlier this month, the Biden administration released 2 reports that outline a national research action plan for the condition and describe federal services available to address the longer-term effects of the pandemic, including long COVID and related conditions. 

But without a standardized definition or treatment protocols for long COVID, patients, healthcare workers, and insurers are left wondering how to proceed with care and recovery. Some are turning to unproven treatments and theories about potential underlying causes of the condition, including the hypothesis that tiny, persistent blood clots could be contributing to the wide array of symptoms. Additionally, without workplace protections, universal health care, and adequate medical support, adults with long COVID sometimes are forced to leave their jobs or incur enormous medical debt. In a new report, the Brookings Institution estimates that around 16 million US residents of working age (18 to 65 years old) have long COVID, and 2 million to 4 million of those are out of work due to the condition. The annual cost of those lost wages is estimated to be around US$170 billion annually, and as high as US$230 billion, according to the report, which warns that without sufficient policy actions, those impacts could worsen over time. 

In related news, long COVID may be less common among pediatric COVID-19 patients than feared. A study published August 22 in JAMA Pediatrics reported a low burden of PASC among study participants, with only 3.7% of children with COVID-19 experiencing at least 1 systemic, syndromic, or medication feature of PASC when compared with children without COVID-19. The researchers noted that the risks of PASC were higher among participants who had more severe SARS-CoV-2 infection, were younger, or had comorbid complex underlying chronic diseases.

UK COVID-19 MORTALITY The UK is reporting considerably higher COVID-19 mortality in summer 2022 than in 2021. From June 8 through August 12, the UK’s COVID-19 mortality was nearly twice the total from the same period last year. During that span, the UK reported more than 5,700 COVID-19 deaths in 2022, compared to 2,936 in 2021. Overall, the cumulative mortality for 2021 far exceeds the 2022 total to date—65,000 compared to 28,303—however, the data illustrate the severity of the UK’s summer Omicron surge, driven largely by the BA.5 subvariant. In June 2021, the UK had reached the end of its Alpha wave, and the Delta variant of concern (VOC) emerged as a major driver of transmission. In contrast, the BA.5 subvariant grew quickly to predominance in June in the UK and essentially spanned the entire summer. Consistent with the trends over the course of the pandemic, the vast majority of UK COVID-19 deaths in summer 2022 were among older adults. Notably, nearly half of the summer 2022 deaths were among adults aged 85 years and older, compared to 27% in 2021, and there were 77% more deaths among adults aged 75-84 years than the same period in 2021.

The UK also suffered a historic heatwave this summer, which may have contributed to the elevated COVID-19 mortality. During 3 “heat periods” in July, the UK reported overall increases in deaths nationwide—ie, all deaths, not only COVID-19. The average daily mortality during these periods (1,224 deaths per day) was 7% higher than the rest of the month. On July 19 alone, when temperatures in the UK exceeded 40°C/104°F for the first time in history, the UK reported 1,775 deaths, more than 50% higher than the average during non-heat periods. Beyond the overall mortality trends related to the heat, data from the UK’s Office of National Statistics (ONS) shows spikes in COVID-19 deaths corresponding to periods of unusually high temperatures. Specifically, daily COVID-19 deaths were nearly one-third higher during 3 “heat periods” in July, compared to other days that month. Older adults tend to be particularly vulnerable to the effects of heat waves, which could potentially account for some of the increased COVID-19 mortality on those days. Further study is required in order to determine any link between the record temperatures and COVID-19 mortality.

REGULATORY PRESSURE According to a new report from the US House Select Subcommittee on the Coronavirus Crisis, senior officials in the administration of former President Donald Trump, as well as outside allies, pressured the US FDA to authorize SARS-CoV-2 vaccines on an accelerated timeline, prior to the November 2020 election, and to authorize or reauthorize ineffective and potentially dangerous treatments for COVID-19, particularly the antimalarial drug hydroxychloroquine touted by Trump. The committee reviewed emails and texts and heard testimony from high-ranking officials to understand the extent of political interference with the federal public health response to COVID-19. Importantly, there is no evidence that administration or outside efforts changed FDA decisions on vaccines, hydroxychloroquine, or any other therapies.