EPI UPDATE The WHO COVID-19 Dashboard reports 630.6 million cumulative cases and 6.58 million deaths worldwide as of November 10. Global weekly incidence dropped for a third week, falling nearly 12% compared with the previous week, to 2.2 million new cases. Weekly incidence fell over the previous week in Europe (-32.5%) and the Eastern Mediterranean (-11%) and remained relatively steady in the Americas (-3%). The South-East Asia (+28%), Western Pacific (+10%), and Africa (+9%) regions experienced increasing weekly incidence. Global weekly mortality decreased slightly from the previous week, down 9%, reaching the lowest level since mid-June 2022.
The US CDC is reporting 97.6 million cumulative cases of COVID-19 and 1.07 million deaths. Incidence for the week ending November 2 rose slightly over the previous week, rising to 273,110 from 260,830 for the week ending October 26. Weekly mortality remained relatively steady for the week ending November 2, down slightly to 2,504 reported deaths from 2,581 deaths the week ending October 26.**
**The US CDC updates weekly COVID-19 data on cases and deaths on Thursdays by 8pm ET.
Both new hospital admissions rose 6.2% over the past week, while current hospitalizations remained stable, falling slightly by 0.4%.
The BA.5 sublineage is quickly losing dominance in the US, accounting for 39.2% of sequenced specimens. The Omicron sublineages BQ.1.1 (18.8%) and BQ.1 (16.5%) are exhibiting growth advantages over other sublineages, including BA.4.6 (9.5%) and BF.7 (9%). Several other Omicron sublineages continue to exhibit increasing or steady trends, including BA.5.2.6 (3.1%), BA.2.75 (2.3%), and BA.2.75.2 (1.3%).
DECLINE IN GLOBAL DEATHS The number of global deaths due to COVID-19 has dropped 90% compared to nine months ago, according to the WHO. WHO Director-General Dr. Tedros Adhanom Ghebreyesus this week said the total number of COVID-related deaths reported during the first week in November was slightly more than 9,400, while the number of global weekly deaths in February rose as high as 75,000. The large drop in COVID-19 deaths is cause for optimism, Dr. Tedros said, but he urged governments to remain vigilant. Low global testing rates, waning surveillance activities, vaccination gaps between high-income countries and low- and middle-income countries, and newly emerging SARS-CoV-2 variants could lead to a resurgence in cases.
MASKING IN SCHOOLS A study published November 9 in the New England Journal of Medicine examining universal masking requirements in Boston, Massachusetts, greater metropolitan area schools found that the lifting of those requirements was associated with an additional 44.9 COVID-19 cases per 1,000 students and staff (95% CI, 32.6 to 57.1), corresponding to an estimated 11,901 cases and to 29.4% of the cases in all districts, in the 15 weeks after universal masking ended. Infection rates were lower among schools that required masking compared with those that did not, even in the area’s public schools that are often in older buildings with poor ventilation systems, more crowded, and attended by students more often from communities considered to be at-risk. The findings add to evidence underlining the importance of public health mitigation measures to prevent the spread of SARS-CoV-2—and possibly other respiratory viruses—in schools, including universal masking requirements.
PFIZER-BIONTECH BA.4/5 BOOSTER Pfizer and BioNTech released new data last week suggesting their updated Omicron BA.4/BA.5-adapted bivalent vaccine booster offers increased antibody response against the current most commonly circulating variants in populations aged 55 and older. Federal officials hope the news of more significant protection against COVID-19 will encourage people to get the booster shot, as less than 9% of the US population has done so. In a letter published in the New England Journal of Medicine, researchers from Israel detailed data from a 6-month follow-up of more than 11,000 healthcare workers who had 4 doses of the Pfizer-BioNTech vaccine. According to the research, participants had good neutralizing antibody responses, equivalent to those seen after a third dose, but that protection waned more quickly than after the third dose, waning completely after 13 weeks. The researchers said their findings suggest that boosters should be timed wisely to align with projected disease waves or be made seasonally available, similar to influenza vaccination.
Health regulators in the UK approved Pfizer-BioNTech’s bivalent booster targeting Omicron BA.4/5 this week for individuals aged 12 years and older, following the US, Canada, and the European Union. The UK already approved bivalent boosters from Pfizer-BioNTech and Moderna targeting Omicron BA.1. The UK also expanded the conditional marketing authorization for Novavax’s Nuvaxovid (NVX-CoV2373) as a homologous and heterologous booster dose after a primary vaccine series of any authorized SARS-CoV-2 vaccine. Novavax this week said a version of its vaccine targeting Omicron BA.1 (NVX-CoV2515) showed a strong immune response as the fourth dose.
In other vaccine-related news, AstraZeneca announced this week the company has withdrawn its application for authorization of its SARS-CoV-2 vaccine in the US due to waning demand and the availability of other vaccines.
COMBINATION COVID/FLU VACCINE Pfizer and BioNTech announced last week they are once again partnering to test a new vaccine candidate—an mRNA-based combination SARS-CoV-2 and influenza vaccine that incorporates the current bivalent SARS-CoV-2 vaccine with a new quadrivalent influenza vaccine candidate called qIRV (22/23). The Phase 1 trial, which has already begun and aims to enroll 180 healthy volunteers between the ages of 18-64 years in the US, will assess the vaccine candidate’s ability to generate immune response, safety, and tolerability.
In addition to the Pfizer-BioNTech candidate, Moderna and Novavax also are developing combination SARS-CoV-2 and influenza vaccines. If any of the vaccine candidates under development are successful, it would relieve people from the burden of scheduling and receiving separate annual shots for 2 respiratory diseases. Health experts hope an mRNA-based influenza vaccine might improve immune responses in older adults. If successful in trials, a combination vaccine could be ready for use during the 2023-2024 flu season.
THERAPEUTICS The United States is heading into a third pandemic winter with uncertainty surrounding several existing treatments for COVID-19 and few options to boost immune protection for immunocompromised individuals. While there is an updated bivalent vaccine booster, uptake is low; only 8.4% of the US population aged 5 years and older have received the shot. Notably, new data show the newer SARS-CoV-2 Omicron subvariants—including BQ.1, BQ.1.1, XBB, and XBB.1—can evade both vaccine-induced and infection-derived immunity. Additionally, the new sublineages are skirting the protection of the remaining monoclonal antibody therapies, including bebtelovimab, used as a treatment for people at high-risk of severe disease, and Evusheld, given prophylactically to people with compromised immune systems. The newer variants also have multiple pathways that could lead to resistance to the antiviral Paxlovid, one of the most effective treatments available, according to research published in Nature.
As the virus continues to develop ways to skirt available therapeutics, stronger efforts are needed to develop and authorize new drugs. Scientists are examining several new strategies, including targeting the human proteins SARS-CoV-2 uses to reproduce. A study published November 4 in Clinical Infectious Diseases showed that twice daily oral zinc supplementation decreased the 30-day death and ICU admission rate and shortened symptom duration among COVID-19 patients. This week, the US FDA issued an emergency use authorization (EUA) for anakinra (Kineret) injection for the treatment of COVID-19 in certain hospitalized patients at risk of developing severe respiratory failure. Anakinra is an interleukin-1 (IL-1) receptor antagonist currently FDA-approved to treat other conditions, including rheumatoid arthritis. On November 9, an FDA advisory panel voted against authorizing an oral drug, sabizabulin, to treat high-risk hospitalized patients with COVID-19. The panel voted 8-5 against the drug’s use, citing concerns over efficacy and safety data being based on a small clinical trial and hinting that it might reconsider additional data gathered from a larger trial. The FDA is not obligated to follow the panel’s recommendations, although it usually does.
In related news, a preprint study from researchers with the US Veterans Health Administration suggests that taking Paxlovid to treat COVID-19 may reduce the risk of later developing post-acute sequelae of SARS-CoV-2 (PASC), commonly called long COVID. The analysis, which has not yet been peer-reviewed, showed that people treated with Paxlovid within 5 days of a positive test were 26% less likely to develop many long COVID symptoms—including cardiovascular issues, hematologic disorders, neurocognitive impairment, fatigue, and trouble breathing—1 to 3 months after testing positive, compared with people who took a placebo. The study has several limitations, including that most of the people included were White and male. Last month, the US NIH announced it is beginning a study to evaluate Paxlovid as a treatment for people already experiencing long COVID.
ENDING COVID-19 PUBLIC HEALTH THREAT A peer-reviewed research article seeking consensus on how to end the COVID-19 public health threat was published November 3 in the journal Nature. The study convened a panel of 386 experts from academia, health settings, nongovernmental organizations, and governmental organizations from 112 countries and territories to develop the recommendations. Using the Delphi study methodology—a method used to identify consensus views across subject matter experts—the research presents a set of 41 consensus statements and 57 recommendations. In an opinion piece published in STAT, a group of the panel’s co-chairs noted that the process of developing, and agreeing on, the recommendations took approximately 14 months and discussed feeling discouraged at times, because world leaders and the general public seemed ready to move on from a problem that still needs solutions.
Some of the highest-ranking recommendations from the study call for “whole-of-society” and “whole-of-government” approaches to ending the COVID-19 health threat. Other recommendations include calling on governments to improve communication, rebuilding public trust, and engaging with communities while managing the pandemic response. The authors mention that improved indoor air quality is needed, in the form of enhanced air filtration and ventilation, in public spaces to prevent the spread of airborne diseases like COVID-19. Mechanical interventions like enhanced filtration and ventilation can prevent the spread of disease without relying on the actions of individuals. Indoor air quality has received more focus internationally since the start of the COVID-19 pandemic, and some world leaders are taking steps to push for improvements. It remains to be seen if world leaders and the general public will heed the advice from the panel.
CHINA The Chinese government today reaffirmed its commitment to its "dynamic zero" COVID-19 policy, despite growing frustrations from Chinese citizens and heavy economic impacts. This week, the number of new COVID-19 cases in China reached a six-month high, prompting public health officials to reinstate lockdowns, frequent testing, and travel restrictions in some areas, frustrating both Chinese residents and the international community. The country’s restrictions are also interrupting the global economy. China’s 1.4 billion people largely lack immunity due to low infection rates, and Chinese-made vaccines have proven less effective against newer, more transmissible SARS-CoV-2 variants, challenging the nation’s exit from its zero COVID policies.
CORRECTION Due to an editing oversight, a story in last week’s report misrepresented research on nasal vaccines and other experimental compounds that might be used to prevent SARS-CoV-2 infection. Errors in the following paragraph contained in the story Non-Needle Vaccine Administration, which can be read in full here, were corrected to state:
Researchers around the world are investigating another non-needle application, nasal vaccines administered through drops or sprays. 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. Some compounds under investigation that are delivered intranasally differ from traditional vaccines, however, in that they provide short-lived protection aimed at blocking a virus’s ability to enter cells rather than building long-term immunity. They would require frequent application to fully coat the surface where viruses could infect cells and likely would need to be used on a regular basis.