EPI UPDATE The WHO COVID-19 Dashboard reports nearly 603.7 million cumulative cases and 6.48 million deaths worldwide as of September 7. Global weekly incidence decreased for the fourth consecutive week, down 11% from the previous week. Global weekly mortality decreased for the third consecutive week, down 10.5% from the previous week.

Regional trends in weekly incidence and mortality also are declining. All regions reported decreases in weekly incidence, ranging from -9% to -29% from the previous week. Weekly mortality is declining in all regions except the Western Pacific (+4.5%) and Africa (+15.6%). 

UNITED STATES

The US CDC is reporting 94.8 million cumulative cases of COVID-19 and 1,043,171 deaths. Average daily incidence continues to decline, down to 74,803 on September 6 from 88,286 on August 30—the lowest average since the beginning of May. Average daily mortality continues to decline, down to 336 on September 6 from a recent high of 495 on August 12.**

**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 6.6% and 7.4%, 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 88.6% of sequenced specimens in the US. While BA.5 remains the overwhelmingly dominant Omicron subvariant, the prevalence of the BA.4.6 sublineage is increasing. BA.4.6 remains the #2 subvariant nationwide, now accounting for 8.4% of sequenced cases, while BA.4 now accounts for 2.8% of cases. Collectively, the remaining variants account for only 0.2% of cases nationally. All variants reported here are sublineages of the Omicron variant of concern (VOC).

EMERGENCY SPENDING REQUEST The Biden administration on September 2 asked the US Congress to pass US$47.1 billion in new emergency spending as part of a continuing resolution to keep the government open beyond the end of the 2022 fiscal year on September 30. The request includes US$22.4 billion to address the ongoing COVID-19 pandemic, of which US$18.4 billion would go to the US HHS to purchase vaccines, treatments, and diagnostics and conduct research, and US$4 billion would support the global response. The federal government is running out of money for its COVID-19 efforts ahead of a potential fall surge, and Congress has been reluctant to authorize additional spending, with Republican lawmakers insisting that new funding be offset by budget cuts or come from transfers of unspent, previously approved US$5 trillion in pandemic relief funds. The new request is already facing opposition in Congress.

Last week, the White House Office of Science and Technology Policy (OSTP), in collaboration with other relevant government agencies, released the First Annual Report on Progress Towards Implementation of the American Pandemic Preparedness Plan, detailing the nation’s pandemic preparedness efforts, including areas for investment. Notably, the report calls the COVID-19 emergency a “moderate pandemic,” despite more than 1 million US deaths and nearly 6.5 million worldwide, and urges the US government to “seize the moment” to prepare for the likelihood of future pandemics and increasing frequency of biological threats. 

UPDATED VACCINE BOOSTERS Last week, the US CDC recommended the use of updated COVID-19 booster vaccines for US residents over the age of 12 who have completed at least a 2-dose primary vaccination series. The recommendation was given to the Pfizer-BioNTech and Moderna mRNA bivalent vaccine boosters that are adapted to address both the original SARS-CoV-2 strain and the Omicron variant of concern, specifically targeting the BA.4 and BA.5 subvariants. The process the companies’ used to modify their vaccines is similar to that of the annual alteration of influenza vaccines. The nimbleness with which scientists can “plug-and-play” variant-specific components into the mRNA platform allowed the rapid updates. However, some individuals have expressed concern over a lack of human clinical data supporting the booster authorizations. 

The bivalent boosters are already available for individuals looking to recharge their immune protection against currently circulating variants ahead of what some officials predict will be a surge of cases this fall and winter. Individuals aged 12 and older are eligible for the new booster at least 2 months after completing their 2-dose primary series or their most recent booster. Anyone who is vaccinated and recently recovered from COVID-19 should wait at least 3 months to get their next shot to maximize their immune response. The new boosters are being offered alongside influenza vaccines, with hopes that immunization coverage will increase for both flu and COVID-19. Countries in the southern hemisphere, including Australia, recently experienced a challenging flu season, prompting health officials to call for increased vaccine coverage before influenza activity increases in the United States. Many top US health officials are suggesting that COVID-19 booster shots will become annual vaccinations, similar to those for influenza. Scientists are still hopeful that future COVID-19 vaccines will enable a more durable immune response, but they also note that the current vaccines provide excellent protection from severe disease. 

Internationally, the UK has approved bivalent boosters targeting Omicron BA.1 from both Moderna and Pfizer-BioNTech for individuals aged 12 and older. Notably, the UK Health Security Agency (UKHSA) this week said healthy children between the ages of 5-11 years will no longer be offered vaccination against COVID-19, angering some parents and healthcare providers. The European Union has also backed both the Pfizer-BioNTech and Moderna Omicron BA.1-adapted boosters. With the rollout of the new boosters, questions are being raised about remaining stockpiles of old formulations. US officials are debating whether or how to use remaining doses, with some worrying that millions of doses might be wasted. International donations are under consideration, although officials are worried about depleting national stockpiles and falling global demand for the vaccines. 

NEEDLE-FREE VACCINES Many scientists and health organizations, including the WHO, have suggested that vaccines delivered nasally or orally may be a crucial step in controlling COVID-19. While the current COVID-19 vaccines, which are administered via intramuscular injection, have shown prolonged effectiveness at preventing severe disease, they are less effective at limiting disease transmission. Many theorize that vaccines administered through nasal drops or oral inhalation may lead to heighted mucosal immunity, a factor that could prolong immunity.

Leading these efforts, both China and India this week approved new needle-free COVID-19 vaccine candidates. China approved the Convidecia Air vaccine made by CanSino Biologics as a booster dose for those who are already fully vaccinated. The vaccine, which is based on the same adenovirus platform as the company’s injected vaccine, is delivered orally via an inhaled mist produced by a nebulizer. India regulators approved a 2-dose primary series vaccine produced by Bharat Biotech, which is administered as drops in the nose. Neither CanSino nor Bharat Biotech have published clinical trial results on the vaccines in peer-reviewed journals, but in-country regulators used preliminary data for their approvals. It is unclear how successful these vaccines will be at preventing disease, but they are a sign of a potential next step for COVID-19 vaccines.

PAXLOVID REBOUND DATA A letter published September 7 in the New England Journal of Medicine provides new data on the occurrence of viral load rebound among COVID-19 patients taking Paxlovid. The data come from a phase 2/3 double-blind, randomized, controlled clinical trial involving nearly 2,250 unvaccinated individuals who had symptomatic COVID-19 infections and at least one risk factor for severe disease. Results regarding viral load rebound were similar in both the treatment and placebo groups, even after controlling for various factors. For those participants for whom viral load data were available, 2.3% of 990 who received Paxlovid experienced viral load rebound between baseline and 14 days after the start of treatment, and 1.7% of 980 patients in the placebo group had viral load rebound within the same timeframe. According to the researchers, the data reaffirm the effectiveness of Paxlovid at preventing severe disease and death, with little difference in instances of rebound between those who took Paxlovid and those who did not. However, Paxlovid remains out of reach for many people who reside in low- and middle-income countries (LMICs), further increasing global disparities in managing COVID-19 disease. 

ANTIBODIES Vaccines against COVID-19 are effective at preventing severe illness and death among most individuals, but new SARS-CoV-2 variants are able to circumvent some immune protection induced by these vaccines, which has necessitated the development of new boosters. Additionally, monoclonal antibody therapies, or mAbs, that worked against earlier variants struggle against current variants. Most recently, data in a preprint study posted to bioXiv show that the 2 mAbs that comprise AstraZeneca’s Evusheld—the only therapeutic antibody combination available to protect immunocompromised people against COVID-19—may be less effective against the BA.4.6 subvariant, which is increasing in prevalence. Increased efforts to keep antibody treatments current and updated are important so that immunocompromised people can access reliable and effective treatments against COVID-19.

Two recent studies point to promising new antibodies that could potentially neutralize all SARS-CoV-2 variants and render boosters unnecessary. In a study published August 5 in Communications Biology, Israeli scientists at Tel Aviv University sequenced B cells from the blood of people who had recovered from COVID-19 in Israel and isolated 2 antibodies, TAU-1109 and TAU-2310, that neutralized 84-90% of the Omicron (B.1.1.529) variant and 90-97% of the Delta variant. These findings were successfully corroborated by researchers at the University of California San Diego and Bar-Ilan University. Researchers noted that monoclonal antibodies that prevent SARS-CoV-2 from binding to ACE2 receptors in human cells—a process that current vaccines target—are more susceptible to viral evolution. The 2 TAU antibodies, named after Tel Aviv University, bind to a different part of the virus’ spike protein than most other mAbs.

In another study, published August 11 in Science Immunology, researchers from Boston Children’s Hospital and Duke University modified a humanized mouse model to develop SP1-77, an antibody that can neutralize all currently known variants of SARS-CoV-2. This model initially was developed to look for antibodies that neutralize HIV, another RNA-based virus that mutates often. Instead of blocking SARS-CoV-2 from binding to ACE2 receptors in human cells, the SP1-77 antibody blocks the virus from fusing its outer membrane with human cell membranes. Though this work is in an early proof-of-concept stage, the researchers have applied for a patent for the SP1-77 antibody and mouse model used to create it. 

LONG COVID/PASC Myriad questions remain over the long-term health implications of SARS-CoV-2 infection, with an estimated 16 million US residents of working age experiencing symptoms of COVID-19 lasting 4 or more weeks beyond acute infection—a condition often called post-acute sequelae of SARS-CoV-2 (PASC) or long COVID. An ad hoc collaboration of healthcare providers from at least 40 long COVID clinics are trying to fill the knowledge gaps, meeting regularly to compare their experiences treating patients who are often frustrated, and sometimes anxious and depressed, with being dismissed by primary care and specialist providers. The American Academy of Physical Medicine and Rehabilitation collaborative is concerned both the public and the Biden administration are losing focus on the pandemic and its potential long-term impacts. The Biden administration has published 2 reports on long COVID, and congressional lawmakers have introduced several bills on the issue, but until more money, research, guidance, and education is available for those treating the condition, healthcare providers worry the lack of attention will further expose the fragility of the nation’s healthcare system and cases will go undertreated or undiagnosed, particularly in underserved communities.

Few risk factors for long COVID have been identified, although many studies suggest conditions such as immunosuppression, hypertension, obesity or older age are associated with a higher risk of severe outcomes. A new study published September 7 in JAMA Psychiatry suggests that psychological distress prior to infection may be a risk factor for post-COVID-19 conditions. The prospective observational cohort study included nearly 55,000 survey respondents, mostly White and female, and examined whether pre-infection psychological distress early in the pandemic—such as depression, anxiety, loneliness, perceived stress, and worry—was associated with an increased likelihood of developing post-COVID-19 conditions among individuals who were later infected with SARS-CoV-2. The researchers found that all types of distress were significantly associated with an increased risk of long-lasting COVID-19 symptoms, even after adjusting for various demographic and health factors. The relationship was dose-dependent, meaning individuals who reported more types of distress were at higher risk of developing long COVID. The authors emphasized that the findings should not be taken to mean long COVID symptoms are psychological and suggested future research should look at biobehavioral mechanisms linking psychological distress with persistent symptoms. 

ORPHANHOOD & CAREGIVER LOSS The COVID-19 pandemic has taken a significant toll on children, many of whom have lost parents and caregivers as a result of COVID-19-related mortality. A research letter published September 6 in JAMA Pediatrics analyzed excess COVID-19-related deaths, estimating that 10.5 million children lost their parents or caregivers to COVID-19 and 7.5 million children experienced orphanhood between January 1, 2020, and May 1, 2022. This is nearly double previous estimates. The study also concluded that the highest amount of orphanhood by primary and/or secondary caregiver loss was found in Southeast Asia (40.6%) and Africa (24.3%). The Imperial College London’s COVID-19 Orphanhood Calculator is updated daily to provide national, regional, and global estimates of children who have lost a parent or caregiver.

There has been a greater push to address the associated economic, social, mental, and health-related consequences that orphanhood and caregiver loss can have on children, particularly as a result of COVID-19-related mortality. In the regions most affected by parent and caregiver loss, aid workers have noticed an increase in issues like child trafficking, early marriage, and exploitative labor practices involving children. The study’s authors recommend the following to mitigate the toll of parent and caregiver loss on children: accelerating vaccination, containment, and treatment efforts to prevent caregiver loss; preparing families to provide safe and nurturing alternative care; and bolstering economic support, violence prevention, parenting support, and school access initiatives. Others recommend funding support programs, such as providing conditional cash transfers to families to ensure that bereaved children continue going to school and remain connected to community resources. Many experts recommend turning to previous research of children who experienced parent and caregiver loss due to the HIV/AIDS epidemic to help identify meaningful solutions.

The United States is one of few countries to have made national commitments to address parent and caregiver loss; the White House released a memorandum in April 2022 promising that families affected by parent and caregiver loss would be able to access necessary support programs and resources. However, there have been no federal efforts to address the needs of children who have lost parents and caregivers as a result of COVID-19. 

PANDEMIC LOCKDOWNS Most researchers agree that the rapid onset of the COVID-19 pandemic gave governments little option but to restrict their population’s interactions in early 2020, and those lockdowns likely helped to curb related deaths. But the restrictions had clear costs, including losses in educational gains, and debate remains over the usefulness of lockdown measures implemented after the outbreak’s initial phase. Now, much of the cost-benefit analyses involve value judgments, making lockdowns difficult to study and leading to disagreements. In China, which continues to enforce its “dynamic zero COVID” policies with what is beginning to appear as endless cycles of strict lockdowns and testing measures, experts agree that the restrictions likely will lead to long-lasting political, economic, and social consequences. The country’s leadership seems committed to these highly disruptive methods in an attempt to eradicate COVID-19, while the rest of the world is learning to live with the novel virus. Currently, nearly every Chinese province has recorded infections in recent days, and more than 300 million residents have been placed under partial or full lockdown since the end of August, some indefinitely. These recent actions have left China’s residents scared, frustrated, and feeling helpless.