COVID-19 Situation Report
Editor: Alyson Browett, MPH

Contributors: Clint Haines, MS; Natasha Kaushal, MSPH; Amanda Kobokovich, MPH; Christina Potter, MSPH; Matthew Shearer, MPH; Marc Trotochaud, MSPH; and, Rachel A. Vahey, MHS.
EPI UPDATE The WHO COVID-19 Dashboard reports 244.9 million cumulative cases and 4.97 million deaths worldwide as of October 28. Global weekly incidence increased by 4.81% compared to the previous week, and mortality increased by 5.27%. After falling the previous week, these increases show the curve trending upward again, with numbers of new cases and deaths close to where they were at the end of September.

Global Vaccination
The WHO reported 6.7 billion cumulative doses of SARS-CoV-2 vaccines administered globally as of October 25. A total of 3.8 billion individuals have received at least 1 dose, and 2.85 billion are fully vaccinated. Analysis from Our World in Data indicates that the overall trend in global daily vaccinations reached a recent high on October 23 at 28.3 million and are beginning to fall again, down to 23.67 on October 27.* The global trend continues to closely follow Asia. Our World in Data estimates that there are 3.85 billion vaccinated individuals worldwide (1+ dose; 48.97% of the global population) and 2.99 billion who are fully vaccinated (37.79% of the global population).
*The average daily doses administered may exhibit a sharp decrease for the most recent data, particularly over the weekend, which indicates effects of reporting delays. In an effort to reflect the longer-term trends, the numbers reported here may not correspond to the most recent data.

The US CDC reports 45.57 million cumulative COVID-19 cases and 737,990 deaths. The current daily incidence average is approximately 68,151 new cases per day and appears to be increasing. Daily mortality appears to be falling again, with an average of 1,098 as of October 26.* 
*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.

US Vaccination
The US has administered 416.2 million cumulative doses of SARS-CoV-2 vaccines. The daily vaccination trend could be beginning to rise again after falling since October 1, with an average 638,768 vaccines administered as of October 22.* We might expect to see increases in this number after the US government last week authorized booster doses for tens of millions more people. There are 220.9 million individuals who have received at least 1 vaccine dose, equivalent to 66.5% of the entire US population. Among adults, 79.7% have received at least 1 dose, as well as 14.9 million adolescents aged 12-17 years. A total of 191 million individuals are fully vaccinated, which corresponds to 57.5% of the total population. Approximately 69.1% of adults are fully vaccinated, as well as 12.45 million adolescents aged 12-17 years. Since August 13, 14.4 million fully vaccinated individuals have received a booster or additional dose of vaccine, including 19.2% of fully vaccinated adults aged 65 or older.
*Due to delays in reporting, estimates for the average daily doses administered are less accurate for the most recent 5 days. The most current average provided here corresponds to 5 days ago.

PEDIATRIC VACCINE As expected, the US FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on October 26 voted to recommend the regulatory agency issue an Emergency Use Authorization (EUA) for the Pfizer-BioNTech vaccine to be available for 28 million US children aged 5 to 11 years. The vote was 17 in favor with one abstention. The FDA is expected to follow the panel’s advice in the coming days, although it is not bound to do so. After the FDA’s decision, the US CDC’s Advisory Committee on Immunization Practices (ACIP) will take up the issue at its next meeting, scheduled for November 2-3. The CDC Director would then issue the agency’s final guidance, potentially making pediatric vaccinations available by the end of next week. The US government has 15 million doses ready to immediately ship to states for distribution to pediatrician offices, hospitals, and pharmacies, and Pfizer-BioNTech announced today that the US has purchased an additional 50 million pediatric doses, which are one-third the dose of the version authorized for people aged 12 and older. Researchers say a SARS-CoV-2 vaccine for children will save lives in that age group and could help keep overall case counts lower, especially if a new variant of concern emerges. But some parents remain concerned over the vaccine’s safety. New data from the KFF COVID-19 Vaccine Monitor show parents of 5- to 11-year-olds are about evenly split, with about 30% saying they will get the shots for their children, one-third saying they will wait, and 30% saying they will definitely not allow their children to get the vaccine.

FOURTH DOSE FOR SOME WITH IMMUNOCOMPROMISE The US CDC updated its guidance on SARS-CoV-2 vaccine booster doses for people who are moderately or severely immunocompromised. Those individuals who received an initial 2-dose series with an mRNA vaccine (Pfizer-BioNTech or Moderna), followed by a third, or “additional,” dose after ≥28 days, may receive a fourth shot—this one considered a booster dose versus the additional dose—at least 6 months after the third dose with any available booster dose (full dose of Pfizer-BioNTech or J&J-Janssen or half dose of Moderna). The agency advised any moderately or severely immunocompromised individual who initially received a single dose of the J&J-Janssen vaccine should receive a single booster dose of any vaccine booster at least 2 months after the initial shot. Notably, if the person initially received the J&J-Janssen shot, they should not receive more than 2 vaccine doses at this time. An estimated 2% of the US population—about 9 million people—are considered to be moderately or severely immunocompromised.

PANDEMIC CONTINUES During its ninth meeting regarding COVID-19, a WHO Emergency Committee of advisors agreed that the pandemic is “far from finished,” 21 months after the group initially named the disease a public health emergency of international concern (PHEIC). Noting that progress has been made in combating the virus, the group called on the international community to use all available tools to mitigate the pandemic’s impacts and recognized the additional burden on addressing humanitarian emergencies, population migration and displacement, and other crises. The committee also expressed concern over challenges responding to the pandemic in the Africa region, including access to sufficient vaccines, diagnostics, and treatments, as well as adequate surveillance and monitoring capabilities. COVID-19 likely will move from a pandemic to an endemic disease at some point in the future, although experts agree that the benchmarks for determining endemicity are unclear. The WHO Emergency Committee will meet again in 3 months, or sooner as needed, to reevaluate the state of the COVID-19 pandemic.

MERCK LICENSING DEAL Merck and the Medicines Patent Pool (MPP) announced a voluntary licensing agreement that will allow MPP to issue sublicenses to permit manufacturers—mostly in Africa and Asia—to make and distribute Merck’s investigational antiviral COVID-19 treatment in 105 low- and middle-income countries (LMICs), following necessary regulatory approvals. Merck is developing the drug, named molnupiravir, in partnership with Ridgeback Biotherapeutics, which acquired the license for the drug from inventor Emory University. Under the deal, Merck, Ridgeback, and Emory will not receive royalties for sales of molnupiravir in LMICs as long as the WHO continues to classify COVID-19 as a public health emergency of international concern (PHEIC). Merck will continue to make the drug for wealthy nations and some middle-income countries, selling it at significantly higher prices. Merck previously licensed production of molnupiravir to several generic drug manufacturers in India, but made the deal with MPP so as not to rely too heavily on production in a single region. 

Earlier this month, Merck announced interim Phase 3 clinical trial data showing molnupiravir, which is administered orally, reduced the risk of hospitalization or death by about half in people with mild-to-moderate COVID-19. The companies applied to the US FDA for Emergency Use Authorization (EUA), and the European Medicines Agency (EMA) announced this week it launched a rolling review of the antiviral. If approved for use, the easy-to-administer pill will be the first available that does not need to be administered by injection or infusion and could help curb COVID-19 outbreaks and alleviate pressure on healthcare systems by helping people recover at home. Health experts have voiced concerns over the potential for inequitable distribution of molnupiravir, but this deal, and a US$120 million pledge from the Gates Foundation to support access to the drug for lower-income countries, provide some hope that the rollout of the treatment will not follow along the lines of the vaccines.

BIONTECH VACCINE MANUFACTURING IN AFRICA BioNTech, which developed the Pfizer-BioNTech SARS-CoV-2 vaccine, announced this week it has signed agreements with Senegal and Rwanda to build mRNA vaccine manufacturing facilities, with construction on at least one plant to begin mid-2022. Initially, BioNTech will own and operate the facility, which will be able to produce up to 50 million vaccine doses annually, with capacity expected to expand. Dr. Matshidiso Moeti, Director of the WHO Regional Office for Africa, said the state-of-the-art facilities could be “game-changers” for the continent, although much needs to be done on the continent to improve vaccine access. Health advocates welcomed the announcement but said the effort is too little, too late. Only 6% of the African population is fully vaccinated, and only 5 nations—less than 10% of the continent’s 54 countries—will reach the year-end target of fully vaccinating 40% of their people, WHO announced today. The UN also warned that limited access to necessary commodities—such as auto-disable syringes used to administer the Pfizer-BioNTech vaccine—could further slow the vaccines’ rollout in Africa.

MORTALITY TRENDS Overall, the risk of death from COVID-19 increases with age. But according to a working paper published by the World Bank Group, this reality varies depending upon where one lives. In high-income countries, COVID-19 deaths generally are concentrated among people over age 65, with only 11% of both official deaths and excess deaths occurring among people younger than age 65. In the upper-middle-income nations for which data were available, the mortality curve became flatter, with 40% of official deaths and 37% of excess deaths occurring among people younger than 65. Among the lower-middle-income nations that had available data, 54% of official deaths were among those under age 65.* Notably, the US has a much younger profile of death—for both official COVID-19 deaths and excess mortality—than countries with similar income levels, even after controlling for differences in population age distribution. With flatter mortality curves, developing countries face the loss of large numbers of people of working age, many of whom provided income to their families or were caregivers to children or family members. These losses likely will have long-term social and economic impacts on these nations into the future and underline the importance of equitable vaccine and resource distribution to close the gaps between wealthy and poorer nations.
*Data for excess deaths were not available for lower-middle-income countries, and no data were available for any low-income countries.

FLUVOXAMINE A study published in The Lancet Global Health showed the inexpensive antidepressant fluvoxamine lowered the odds of hospitalization and death when administered to COVID-19 patients early in their symptom onset. The trial, conducted in Brazil, included 741 individuals who received fluvoxamine and 756 who received placebo, 58% of whom were female, and the cohort had an average age of 50. The study included only high-risk patients and those who enrolled were largely unvaccinated, raising questions about the antidepressant's applications as a therapeutic among vaccinated individuals. Additionally, the study mentioned that some patients were unable to fully tolerate the intended study dosage, raising concerns about the most beneficial dose. Nonetheless, the study results represent positive news in continuing global efforts to reduce the need for COVID-19 hospitalization in a more accessible manner. The current cost of a 10-day course of fluvoxamine is about $4, significantly lower than many of the options currently used to treat COVID-19. 
AT-HOME RAPID TESTS Earlier this week, the US HHS announced the agency is expanding its efforts to make at-home COVID-19 testing more accessible. HHS will invest US$70 million to help developers move through the regulatory process and develop a plan with the US FDA to streamline authorization decisions in an effort to bring more over-the-counter tests to market. At the federal level, there has been a push to increase the accessibility of at-home diagnostics ahead of the winter season. The administration of US President Joe Biden announced these plans as businesses move closer to having to implement a “vaccinate-or-test mandate.” The goal of the announcements are two-fold: to increase the supply of available tests and potentially lower the price threshold which currently limits their widespread usage. The FDA has authorized several at-home test kits. 

PANDEMIC PREPAREDNESS The Global Preparedness Monitoring Board (GPMB) is warning world leaders that the window of opportunity to address the COVID-19 pandemic and prepare for future disease outbreaks is quickly closing, as the world begins to move on to other pressing issues. In its third annual report, GPMB says the failures of the COVID-19 pandemic response were markedly bogged down by geopolitical divisions and closed-door negotiations that neglected to include key stakeholders. GPMB called for renewed international cooperation and outlined 6 recommendations. In November 2021, the World Health Assembly will hold a special 3-day session to discuss the plausibility of developing a "pandemic treaty." 
In the US, discussions over the federal government’s response to COVID-19 have been sidelined in the US Congress, as negotiations over US President Joe Biden’s domestic agenda and the federal budget take precedence. Efforts to present a bipartisan bill in the US Senate to bolster pandemic preparedness have been postponed until later this year or early 2022. Public health experts are advocating for improvements to data collection systems and supply chain vulnerabilities that continue to present significant challenges during the COVID-19 pandemic. The Biden administration has indicated it is prioritizing global health security, earlier this month releasing an annual report on strengthening the Global Health Security Agenda (GHSA).

FINANCIAL DRAIN ON HOSPITALS The COVID-19 pandemic has exacerbated existing inequities in healthcare systems and exposed disparities in funding allocations. In a recent study published in JAMA, researchers examined how US federal COVID-19 relief funding was allocated, how CARES Act funding was utilized, and disparities in funding allocations. They found that academic-affiliated hospitals, hospitals with higher pre-pandemic assets, and hospitals with higher numbers of COVID-19 cases received higher levels of funding, while critical access hospitals received lower levels of financial assistance. The lack of transparency behind CARES Act funding allocation possibly resulted in resource-limited hospitals suffering under the demands of the pandemic, and the researchers emphasized the need to base funding allocations on hospitals’ pre-disaster finances in future resource allocations. Hospitals also took an economic hit due to the postponement of elective surgeries during the beginning of the COVID-19 pandemic, according to 2 studies presented at a conference of the American College of Surgeons (ACS). One healthcare system lost 42% of its net revenue in 2020 after delaying surgeries from mid-March to July 2020, while US children’s hospitals lost $1.53 billion due to delays or cancellations of pediatric surgeries. The researchers said the results show the need for long-term financial planning and preparations for sustained operations management during crises.