EPI UPDATE The WHO COVID-19 Dashboard reports 628 million cumulative cases and 6.57 million deaths worldwide as of November 2. Global weekly incidence dropped for a second week after remaining steady for 6 weeks, falling 14% compared with the previous week to 2.5 million new cases. Weekly incidence fell over the previous week in Africa (-40%), Europe (-29%), and the Eastern Mediterranean (-8%); remained relatively steady in South-East Asia (-2%); and increased slightly in the Americas (+5%) and Western Pacific (+5%). Global weekly mortality decreased slightly from the previous week, down 4%.
The US CDC is reporting 97.3 million cumulative cases of COVID-19 and 1.07 million deaths. Incidence for the week ending October 26 remained relatively steady over the previous week, rising to 265,839 reported cases from 261,315 cases for the week ending October 19. Weekly mortality also remained relatively steady for the week ending October 26, up slightly to 2,649 reported deaths from 2,591 deaths the week ending October 19.**
**Beginning October 20, the US CDC began reporting and publishing aggregate case and death data, and line level data where applicable, from jurisdictional and state partners on a weekly basis rather than daily. As a result, COVID-19 data on cases and deaths are updated every week on Thursdays by 8pm ET.
Both new hospital admissions and current hospitalizations appear to have leveled over the past week, rising slightly by 2.1% and 0.1%, respectively.
The BA.5 sublineage continues to be the dominant strain in the US, accounting for 49.6% of sequenced specimens, but its estimated prevalence appears to be decreasing more rapidly now. The Omicron sublineages BQ.1 (14%) and BQ.1.1 (13.1%) are exhibiting growth advantages over other sublineages, including BA.4.6 (9.6%) and BF.7 (7.5%). Several other Omicron sublineages continue to exhibit increasing or steady trends, including BA.5.2.6 (2.8%), BA.2.75 (1.8%), and BA.2.75.2 (1.2%).
LONG COVID/PASC Post-acute sequelae of SARS-CoV-2 infection (PASC), commonly referred to as long COVID, continues to pose a heavy yet poorly understood toll on an uncertain proportion of individuals previously infected with SARS-CoV-2. Healthcare providers, scientists, and long COVID patients are hunting for answers regarding the condition, which cuts across all demographic groups and COVID-19 disease severities.
A group of international researchers published a commentary in Nature Reviews Nephrology highlighting recent studies indicating that long COVID increases the risk of adverse long-term kidney events and can have negative effects on the cardiovascular, hematological, and neurological systems, as well as on mental health and glycometabolism. Given the likelihood that long COVID will lead to new noncommunicable diseases in millions of people despite vaccine-mediated protection, the authors call for governments, health systems, and researchers to further investigate prevention and treatment of long COVID, in addition to building health systems capacity for the expected future noncommunicable disease burden. Notably, the US National Institute of Health’s (NIH) RECOVER Initiative has announced a new clinical trial testing Paxlovid as a treatment for long COVID in collaboration with Duke Clinical Research Institute.
A new systematic review from the European Centre for Disease Prevention and Control (ECDC) attempted to better characterize the prevalence of long COVID, stratified by initial COVID-19 disease severity, utilizing recruitment setting as a proxy indicator. Across 74,213 patients from 61 cohort studies in 15 countries assessed at least 12 weeks after initial SARS-CoV-2 infection, at least one long COVID symptom was found in 50.6% (95% CI: 41.1% to 60.2%) of patients recruited in community settings, 66.5% (95% CI: 56.0% to 76.3%) of patients recruited in hospital settings, and 73.8% (95% CI: 62.3% to 83.9%) of patients recruited in intensive care unit (ICU) settings. Prevalence of individual long COVID symptoms (specifically fatigue, shortness of breath, depression, headache, and dizziness) were higher among hospital settings than community settings. While the study only included patients infected pre-Omicron and did not include uninfected individuals as a control, this investigation—one of the largest studies of long COVID—indicates that the burden of the condition is greater than previously estimated and suggests long COVID symptoms may be worse for patients with more severe COVID-19 disease.
Similarly, a study published October 27 in JAMA Network Open assessed the prevalence of COVID-19 symptoms lasting longer than 2 months past infection in 16,091 US survey respondents between February 5, 2021, and July 6, 2022, as well as potential associations between long COVID and sociodemographic factors, prior vaccination status, and predominant variant at the time of infection. According to the results, 14.7% of respondents reported COVID-19 symptoms at least 2 months after infection, reflecting 13.9% of the previously infected US adult population after reweighting. Notably, further analysis indicated that female gender (adjusted odds ratio: 1.91; 95% CI, 1.73-2.13) and older age per decade above 40 years (adjusted odds ratio: 1.15; 95% CI, 1.12-1.19) may be associated with long COVID development, while risk may be less among those who received primary vaccination series prior to infection (odds ratio, 0.72; 95% CI, 0.60-0.86), individuals with a graduate education vs high school or less (adjusted odds ratio, 0.67; 95% CI, 0.56-0.79), and urban vs rural residence (adjusted odds ratio, 0.74; 95% CI, 0.64-0.86). Compared with ancestral COVID-19, infection during periods when the Epsilon variant (OR, 0.81; 95% CI, 0.69-0.95) or the Omicron variant (OR, 0.77; 95% CI, 0.64-0.92) predominated in the US was also associated with lower risk of long COVID symptoms.
VACCINE BOOSTERS With a worrisome mix of SARS-CoV-2 Omicron sublineages expected to drive another cold-weather surge of COVID-19 cases, experts in the US are encouraging people to get vaccinated and boosted using the new bivalent shots. Notably, however, only 7.3% of the US population aged 5 years and older have received the updated boosters, which target both the original SARS-CoV-2 viral strain and the BA.4 and BA.5 Omicron subvariants. Experts expect the new shots to help provide broad protection against these and newly emerging sublineages. Several recent studies posted as preprints—one each from research teams led by scientists from Columbia University Vagelos College of Physicians and Surgeons, Emory University School of Medicine, the University of Texas Medical Branch, and two led by researchers from Beth Israel Deaconess Medical Center—show that the new bivalent BA.5/4 boosters performed as well as or better than the original boosters and have the potential for BA.5 neutralization 4-fold higher than the original booster. These data, taken together with a study published in Science Immunology showing that booster doses (original) help improve neutralizing antibodies without strongly affecting cellular immune responses, further underline the necessity of booster shots to help strengthen waning immunity and protect against severe disease and death from COVID-19.
NON-NEEDLE VACCINE ADMINISTRATION The administration of vaccines through oral or nasal delivery routes offers several probable advantages, including the potential for stimulating immune reactions that could prevent transmission or symptomatic infection. Additionally, needle-free administration could make vaccination more accessible to countries with limited health infrastructure that have struggled with traditional vaccine administration in the past. Plus, those wary of needles could be persuaded to get vaccinated. The Chinese city of Shanghai last week began the rollout of what is believed to be the world’s first inhalable SARS-CoV-2 vaccine. Administration takes less than 20 seconds: a mist containing the vaccine is inhaled slowly through the mouth, then patients hold their breath for five seconds. The CanSino Biologics vaccine was approved in September as a booster dose, but the effectiveness of the inhaled vaccine is not known.
Researchers around the world are investigating another non-needle application, nasal administration. Nasal vaccines, administered through drops or sprays, could offer fast-acting protection, aimed at targeting virus cells where they first take hold in the lining of the nose and throat. Vaccines delivered intranasally differ from traditional vaccines, however, in that they are short-lived compounds aimed at blocking the virus’s ability to enter cells rather than building long-term immunity. They would require frequent application to fully coat the surface where viral cells may enter and likely would need to be used on a regular basis. Regulators in India approved a nasal vaccine in September, but it is not yet in use and efficacy data have not been released. Notably, Oxford and AstraZeneca’s attempt at nasal vaccine administration did not yield significant protection in first-phase human clinical trials. The small trial, which included 30 previously unvaccinated individuals and 12 participants who had received a primary 2-dose vaccination, elicited mucosal membrane antibody responses in only a minority of participants.
A study published October 27 in Science tested an approach the Yale-led researchers dubbed “prime and spike.” The method capitalizes on existing systemic immunity to SARS-CoV-2 gained from primary intramuscular (IM) vaccination to boost the body’s immune response in the respiratory tract using intranasal vaccine delivery. Administered in mice, the nasal spray elicited robust mucosal responses and offered comparable systemic neutralizing antibody booster responses to IM-administered boosters months out from primary vaccination. More research and funding are needed on non-needle vaccines, a key reason why nasal vaccine research has not progressed at the rate of IM-delivered vaccines. In the US, which led the race to develop SARS-CoV-2 vaccines, a lack of funding is preventing promising candidates and methodologies—such as the one tested by Yale researchers—from progressing into human studies and closer to regulatory authorization.
TRAVEL MASK MANDATES The US Supreme Court this week let stand a lower court ruling allowing the Transportation Safety Administration (TSA) to require mask use for travelers on planes, trains, and other methods of transport. The lower court’s ruling, from the US Court of Appeals for the DC Circuit, said the TSA has the authority to maintain safety and security during national emergencies. The TSA dropped its mask mandate in April after a federal judge in a different case ruled the agency had exceeded its authority. As part of a comprehensive strategy, the use of high-quality masks can help reduce the risk of viral transmission, including SARS-CoV-2.
GLOBAL VACCINE ACCESS If SARS-CoV-2 vaccines had been equitably shared among all nations in 2021, 295.8 million infections and 1.3 million deaths due to COVID-19 could have been prevented worldwide by the end of that year, even without any associated changes in behavior, according to a retrospective modeling study published October 27 in Nature Medicine. Additionally, if wealthier nations had kept nonpharmaceutical interventions (NPIs)—such as mask use and limitations on gathering sizes—in place for longer under this scenario, as many as 3.8 million lives could have been saved, the modeling suggests. Vaccine equity has improved globally, although disparities in access persist, according to the WHO. Overall, 68% of the world’s population has received at least one vaccine dose, but that proportion drops to 23% in low-income countries.
Though vaccine access is improving, other challenges remain, including the spread of mis- and disinformation, a lack of laboratory capacity and access, and the need for large capacity storage facilities, among others. Some experts are warning that the emergence of newer variants capable of greater immune evasion could create a critical situation in 2023, particularly in low- and middle-income countries (LMICs) whose populations are undervaccinated. But the situation also provides an opportunity for increased efforts to supply LMICs with next-generation vaccine boosters. Even as access to SARS-CoV-2 vaccines improves, the world needs to seriously look to the future and devise systems that will facilitate the equitable distribution of medical countermeasures during the next disease outbreak.