COVID-19 Situation Report
EPI UPDATE The WHO COVID-19 Dashboard reports 228.4 million cumulative cases and 4.69 million deaths worldwide as of September 21. Global weekly incidence decreased by 8.6% compared to the previous week, and mortality fell by 6.6%.

Global Vaccination
The WHO reported 5.78 billion cumulative doses of SARS-CoV-2 vaccines administered globally as of September 20. A total of 3.30 billion individuals have received at least 1 dose, and 2.39 billion are fully vaccinated. Analysis from Our World in Data indicates that the overall trend in global daily vaccinations continues to decline. After peaking 3 times at more than 42 million doses per day between late June and early September, the average has fallen to 29 million. In mid-July, between the 2 highest peaks, the average dropped as low as 20 million before rebounding, so the longer-term trend remains uncertain*. The global trend continues to closely follow Asia. Daily vaccinations in Europe have steadily declined since early July, and if the continent as a whole continues on this trajectory, it could soon fall below Africa on a per capita basis. On the opposite end of the spectrum, Oceania is currently #1 globally in terms of per capita daily vaccinations. It was second to last (ahead of only Africa) as recently as early July, but its trend has accelerated over the past several months. Our World in Data estimates that there are 3.43 billion vaccinated individuals worldwide (1+ dose; 43.6% of the global population) and 2.51 billion who are fully vaccinated (31.9% 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 42.0 million cumulative COVID-19 cases and 672,738 deaths. The US appears as though it may have passed a peak in terms of daily incidence. The most recent high was 159,929 new cases per day on September 1, and the trend began to decline slightly before the Labor Day holiday weekend. The reporting has largely recovered following the holiday, but the average daily incidence has not returned to the pre-holiday level. The current average is approximately 141,000 new cases per day and appears to be decreasing. Daily mortality continues to increase slowly, now up to 1,521 deaths per day—the highest average since February 27. If the daily incidence peaked on September 1, we would expect mortality to peak in the next week or so*. 
*Changes in state-level reporting may affect the accuracy of recently reported data, particularly over the weekend. In an effort to reflect the longer-term trends, the numbers reported here may not correspond to the most recent dates.

At more than 1,500 deaths per day, the US could surpass 675,000 cumulative deaths in the next several days, which would make the COVID-19 pandemic more deadly in the US than the 1918 influenza pandemic. Notably, the US population in 1918 (approximately 105 million) was less than one-third of the current population, so the COVID-19 mortality is much lower on a per capita basis.

California is the only US state categorized as having Substantial community transmission, having fallen below the threshold of 100 weekly new cases per 100,000 population that corresponds to the High category. California’s test positivity is not reported by the CDC. The next 4 states are reporting between 125-150 weekly new cases per 100k: Connecticut (126.5), Colorado (127.9), Maryland (141.5), and Vermont (146.3).

US Vaccination
The US has administered 386 million cumulative doses of SARS-CoV-2 vaccines. Daily vaccination reporting appears to have recovered from the Labor Day holiday weekend, and the longer-term trend continues to decline from the most recent peak on August 29*. There are 212.0 million individuals who have received at least 1 dose, equivalent to 63.9% of the entire US population. Among adults, 76.5% have received at least 1 dose, as well as 14.4 million adolescents aged 12-17 years. A total of 181.7 million individuals are fully vaccinated, which corresponds to 54.7% of the total population. Approximately 65.9% of adults are fully vaccinated, as well as 11.5 million adolescents aged 12-17 years.
*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.

US FDA PANEL BOOSTER DOSE RECOMMENDATION The US FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on September 17 voted 16-2 against authorizing third doses of the Pfizer-BioNTech SARS-CoV-2 vaccine for the general population, but it unanimously recommended third doses for individuals aged 65 years and older and those who are at elevated risk for severe disease. The panel’s recommendation—made after more than 7 hours of deliberation—is a surprising rebuke to plans previously announced by US President Joe Biden, who expected booster doses to begin for the general population this week. Although the FDA is not required to follow VRBPAC recommendations, it generally does, and both the FDA and the US CDC’s Advisory Committee on Immunization Practices (ACIP) are expected to adopt the recommendation in the coming days and clarify who qualifies for booster doses. VRBPAC also signaled unanimous support for third doses for healthcare workers and others at high occupational risk, but it did not take a formal vote. The panel will likely discuss booster doses for those individuals and individuals who have received the Moderna and J&J-Janssen vaccines at a later date. 

Hours before the VRBPAC meeting, the CDC released data indicating the level of protection against hospitalization wanes significantly in the 4 months following vaccination. The study, published in the CDC’s Morbidity and Mortality Weekly Report (MMWR), showed vaccine effectiveness (VE) against hospitalization for the Pfizer-BioNTech vaccine fell from 91% in the first 4 months to 77% beyond 120 days post-vaccination. For the Moderna vaccine, VE against hospitalization remained high, falling only 1 percentage point (pp) after 120 days, from 93% to 92%. Although there were not enough participants to comparatively evaluate the J&J-Janssen vaccine’s effectiveness over time, the study said the single-dose vaccine has been 71% effective at preventing hospitalization. 

While most health experts applauded the FDA panel’s decision, arguing that it was evidence-based, some US residents expressed confusion over the recommendation. Biden administration officials appeared to backpedal slightly on the previous announcement that booster doses could be made available to the general public beginning this week, with several saying they still expected US health agencies to recommend the extra shots for the general population in the coming weeks when more data become available. There remains significant debate over the need for widespread booster doses. Some experts instead advocate for increased focus on reaching unvaccinated individuals, who account for the majority of new COVID-19 cases in the US, and others call for equitable allocation and distribution of available doses globally. 

J&J-JANSSEN VACCINE SECOND DOSE On September 21, Johnson & Johnson (J&J) announced preliminary findings from a Phase 3 clinical trial that indicate increased protection following a second dose of its SARS-CoV-2 vaccine, developed in collaboration with Janssen Pharmaceuticals. Unlike other major vaccines—including those from Pfizer-BioNTech, Moderna, and AstraZeneca-Oxford—the J&J-Janssen vaccine was originally authorized as a single dose. In the Phase 3 clinical trial, the second dose was administered 2 months after the first dose, and the control group was made up of individuals who received only a single dose. The press release does not indicate the total number of participants.

According to the press release, a second dose increased the vaccine’s efficacy (compared to a single dose) by an estimated 100% against severe disease* and 75% and 94% against symptomatic COVID-19 globally and in the US, respectively. Additionally, antibody levels after the second dose were 4-6 times higher than after a single dose. The study also evaluated a second dose administered 6 months after the first dose. Following a booster 6-month booster, antibody levels increased by a factor of 12 compared to a single dose. The press release does not provide overall efficacy estimates (ie, compared to receiving no vaccine at all). The press release also describes real-world data that indicate the single-dose regimen provides strong, lasting protection against COVID-19. As has been the trend throughout the pandemic, the preliminary findings were presented via press release, and the data have not been published publicly nor subjected to peer review; however, J&J committed to submitting the full dataset for publication “in the coming months.”
*The efficacy against severe disease is based on only 8 cases among the control group and zero among those who received the second dose. The low number of cases yields a large confidence interval (30-100%), and additional data would provide a better understanding of the protective effect.

PEDIATRIC VACCINATION DATA Pfizer and BioNTech on September 20 announced positive results from a Phase 2/3 trial of their SARS-CoV-2 vaccine in children aged 5 to 11 years. The researchers found that a 2-dose regimen of 10µg doses administered 21 days apart demonstrated a favorable safety profile and robust neutralizing antibody response. The findings—which are neither published nor peer-reviewed—are a crucial step toward a SARS-CoV-2 vaccine becoming available for younger children, and the companies expect to submit an application to the US FDA for the vaccine’s authorization for that age group by the end of September. US regulators have issued warnings to the general public to wait for authorization before seeking vaccination for younger children, as the full adult dose of 30µg may put children at a higher risk for adverse side effects, including myocarditis.

The trial included nearly 2,300 children, and two-thirds of them in the vaccine group. The vaccinated children also were compared with a separate cohort of 16-25-year-old individuals who received the full adult course of the vaccine (2 doses of 30µg). The trial found that the neutralizing antibody response was similar between both vaccinated groups, with the neutralizing antibody levels within 5% of each other. Both groups also experienced similar post-vaccination adverse events.

Results from another study evaluating the Sinopharm SARS-CoV-2 vaccine in children were published on September 15 in The Lancet Infectious Diseases. The Phase 1/2 trial examined the safety and immunogenicity of the vaccine in a cohort of children aged 3-17 years, with participants broken into several age groups (3-5, 6-12, and 13-17 years) and dosing groups (0 [control], 2µg, 4µg, and 8µg). Three (3) doses of each vaccine dosage or placebo were administered 28 days apart. All adverse events were categorized as mild or moderate severity, but the article does not report on serious adverse events. The study concluded that children who received the vaccine had robust immune responses and similar levels of neutralizing antibodies to those observed in older vaccine recipients. The study recommended a 2-shot 4µg dose regimen for future Phase 3 trials. Additional data are being collected through a Phase 3 trial currently taking place in the UAE. 

UN GENERAL ASSEMBLY & COVID-19 SUMMIT Beginning with an address to the UN General Assembly today, US President Joe Biden will focus his attention on efforts to end the COVID-19 pandemic and attempt to rally other vaccine-producing nations to commit to providing additional doses to countries in need. In addition to the main UN General Assembly meetings, the US will participate in a virtual COVID-19 summit on September 22 and a meeting of the Quadrilateral Security Dialogue (Australia, India, Japan, US) on September 24. The effort to improve vaccine diplomacy is being watched carefully by public health experts, advocates, and organizations eager for President Biden to fulfill his pledge that the US will serve as an “arsenal of vaccines” for the world. The US, along with several other higher-income nations, has faced criticism for ignoring calls from the WHO to postpone vaccine booster dose programs in order to redirect those shots to the COVAX facility, which is behind schedule on its goal to vaccinate at least 10% of the populations in low- and middle-income countries (LMICs). At the COVID-19 summit, the US is expected to make several announcements regarding its own commitments. Reportedly, the US government is negotiating to purchase an additional 500 million doses of the Pfizer-BioNTech vaccine to distribute globally, which would bring the total US donation to 1.15 billion—about one-tenth of the estimated 11 billion the world needs.

US officials have expressed concern that the UN General Assembly meetings could become a superspreader event, with the world body relying only on an honor system to ensure attendees are vaccinated before they speak. More than 100 heads of state and government as well as more than 20 foreign ministers have registered to speak in person at the meeting, with some already openly defying the vaccine honor system. Brazil President Jair Bolsanaro, for example, said he will decide whether to take the vaccine after everyone in his nation is vaccinated—only 36% is currently vaccinated. Other leaders, including Vietnamese President Nguyen Xuan Phuc, have not disclosed their vaccination status, and Russia complained the requirement infringes upon nations’ rights to participate at the UN. The New York City government, which requires proof of vaccination for convention centers, has said the requirement includes the UN assembly hall, although the UN headquarters building is considered international territory. In a goodwill effort, the municipal government has set up a mobile vaccine clinic outside the UN complex to offer free testing and vaccination.

US AIR TRAVEL REQUIREMENTS The US government plans to ease travel restrictions for fully vaccinated foreign nationals beginning in November, marking the end of an 18-month interruption to international on travel. The US currently prohibits travel for most non-US citizens who have visited Brazil, China, the EU, India, Iran, South Africa, or the UK within the past 14 days. Under the new policy, non-US residents traveling to the US will have to show proof of vaccination and proof of a negative SARS-CoV-2 test within 3 days before boarding a US-bound aircraft. Children not yet eligible for vaccination will be allowed to travel with only a negative test. The US CDC is expected to issue an order directing airlines to collect travelers’ phone numbers and email addresses for a new contact tracing system that will enable health officials to follow up with travelers after they arrive in the US. Additionally, unvaccinated US citizens arriving in the US will need to show proof of a negative SARS-CoV-2 test taken within 1 day of traveling to the US and and also complete another test upon arrival (reportedly, at their own expense). This week, the US extended its restrictions on nonessential travel to Mexico and Canada, but there is no indication if or how the vaccination and testing requirements would be applied at land borders.

VACCINATION IN AFRICA With more than 8 million cumulative COVID-19 cases recorded in African countries and rising concern over a fourth wave, WHO Regional Director for Africa Dr. Matshidiso Moeti on September 19 called on wealthy nations to forego third vaccine doses for healthy individuals, donate excess doses, and allow COVAX and the African Union to purchase the vaccine needed to protect the continent’s population. Writing in a New York Times opinion piece, Dr. Moeti warned that with only 4% of the African population fully vaccinated, countries with low vaccination coverage “could act as variant incubators, increasing the risk that more dangerous variants will emerge and enter international travel networks.” Additionally, the COVAX facility recently announced that it is cutting its planned vaccine deliveries to Africa by 150 million doses in 2021, leaving the continent 500 million doses short of the year-end target of fully vaccinating 40% of the population. According to WHO Africa, the 470 million doses now expected to be delivered this year through COVAX is enough to vaccinate only 17% of the population. At a news conference last week, Dr. Moeti blamed vaccine export bans and vaccine hoarding for the shortfall, arguing that higher-income countries are causing “a chokehold on the lifeline of vaccine supplies to Africa.” She noted that African nations recently tripled the weekly doses administered over previous weeks, but the continent will likely not reach the 40% goal until at least March 2022, based on the current pace. 

INDIA VACCINE EXPORTS India is expected to resume exporting domestically manufactured SARS-CoV-2 vaccines sometime between October and December 2021. Indian Minister of Health Mansukh Mandaviya indicated that the initial focus will be on supplying the COVAX facility and neighboring countries. India is the world’s largest manufacturer of vaccines, but it prohibited exports of SARS-CoV-2 vaccines in April 2021, when the country was experiencing its largest surge. The announcement comes ahead of Prime Minister Narendra Modi’s visit to Washington, DC, for a summit of Quadrilateral Security Dialogue, which includes Australia, India, Japan, and the US. India's monthly vaccine output has increased recently, and the country expects to produce at least 1 billion doses in the last 3 months of 2021.

CANADA VACCINE APPROVALS On September 16, Health Canada granted full regulatory approval to both the Moderna and Pfizer-BioNTech SARS-CoV-2 vaccines for use in individuals aged 12 years and older. In an announcement, Moderna said the approval marks “an important milestone,” as it is the first full approval for its SARS-CoV-2 vaccine. Notably, the Moderna vaccine is not yet authorized in the US for children under the age of 18.

“TEST-TO-STAY” PROTOCOLS With the school year only beginning across the US, already tens of thousands of students have had to quarantine after coming in close contact with classmates or teachers who test positive for SARS-CoV-2. An increasing number of school districts nationwide are implementing testing programs to try to keep more children in classrooms instead of having to quarantine at home—and possibly disrupting their parents’ work schedules and their education—after being exposed to a known COVID-19 case. The strategy, known as “test to stay” or modified quarantine, allows children to stay in school if they remain asymptomatic, participate in regular testing (eg, daily) and continue to test negative, and follow other preventive measures. Typically, the tests and the staff to conduct them are provided by the school districts, straining already-tight resources. 

In a statement to The New York Times, the US CDC said it does not recommend or endorse test-to-stay strategies at this time, saying there is not yet enough evidence to support them. The agency recommends that any unvaccinated student who has close contact with a known COVID-19 case undergo quarantine for 14 days. A study conducted by British researchers and published last week in The Lancet suggests that daily testing of school-based contacts could be effective in mitigating COVID-19 risk while to helping more students stay in school following an exposure. The study showed that COVID-19 incidence rates were not significantly different between schools with "test-to-stay" policies compared with those that required at-home quarantine.

FAKE VACCINATION CARDS Both the price of fake SARS-CoV-2 vaccination cards and the number of online sellers have increased dramatically in recent weeks, following US President Joe Biden’s announcement extending vaccine mandates for most federal workers, healthcare workers, and employees of many US companies, according to cybersecurity company Check Point Software Technologies. As of September 2, the average cost of a fake vaccination card bearing the US CDC logo was US$100, but that price doubled following President Biden’s September 9 announcement. Additionally, the estimated number of vendors increased from approximately 1,200 to more than 10,000. Many of the cards are being sold through the instant messaging app Telegram, which has 500 million monthly users worldwide and exhibited a 10-fold increase in US users following the mandates, up to 300,000. Most sellers require payment in cryptocurrency and collect personal information that is unnecessary to mail a blank fake card. Government authorities have cautioned against providing such information. Though it is unclear how people receive the fake cards, US Customs and Border Protection (CBP) has reportedly intercepted thousands of packages of fake vaccination cards sent to the US from China in recent months. Both the US FBI and CBP have warned that buying, creating, or selling fake vaccination cards is a federal crime.

INACTIVATED VIRUS VACCINE & EGG-BASED MANUFACTURING Researchers in Thailand and the US published (preprint) results from a Phase 1/2 clinical trial of an inactivated recombinant SARS-CoV-2 vaccine. The NDV-HXP-S vaccine* was developed in Thailand, Vietnam, and Brazil, based on components developed at the Icahn School of Medicine at Mount Sinai (New York, US), the University of Texas (US), and it utilizes a Newcastle disease virus (NDV) platform. The trial included 210 participants aged 18-59 years who were randomized into 6 groups. They received 2 injections 28 days apart using either a 1µg dose (with or without an adjuvant), 3µg dose (with or without an adjuvant), 10µg dose (without adjuvant), or placebo. All but 5 participants received both doses. The Phase 1/2 trial was principally designed to evaluate safety, and all doses were generally well tolerated, with no serious adverse events reported. Additionally, 93.9-100% of vaccinated participants had increases in neutralizing antibodies of at least 4 times over baseline, an encouraging indication of immune response.

There are multiple other inactivated virus vaccines already available—including those from Sinopharm and Sinovac in China and Bharat Biotech in India—but the NDV-HXP-S vaccine has the advantage of being produced using chicken eggs, similar to some seasonal influenza vaccines. Facilities around the world have production lines that can manufacture seasonal influenza vaccines using chicken eggs, and a SARS-CoV-2 vaccine that leverages this manufacturing platform could take advantage of substantial and geographically distributed production capacity. As we have covered previously, production capacity for existing SARS-CoV-2 vaccines remains limited, and many countries, particularly in Africa, continue to struggle to access sufficient doses to support their vaccination efforts. It will still take months to complete Phase 3 clinical trials, but a vaccine that utilizes egg-based production could potentially increase vaccine access for low- and middle-income countries (LMICs).
*Unlike previous vaccines and vaccine candidates that were principally developed by 1 or 2 companies or organizations, the NDV-HXP-S vaccine does not have a clear informal designation (eg, Pfizer-BioNTech, Moderna). NDV refers to the Newcastle disease virus platform, and HXP refers to HexaPro, a modified version of the SARS-CoV-2 spike protein used in the vaccine.

ALABAMA Alabama State Health Officer Dr. Scott Harris on September 17 said that the state’s overall mortality rate outpaced its birth rate in 2020 for the first time in recorded history. Alabama recorded 57,641 live births and 64,714 total deaths in 2020. Records from the Alabama Department of Public Health indicate that 7,128 of those deaths were attributable to COVID-19. Historically, Alabama’s birth rate has remained higher than the death rate, even during high-casualty tragedies such as World War I, World War II, and the 1918 influenza pandemic. This unfortunate statistic highlights the devastating toll the current pandemic has inflicted on vulnerable areas of the nation. Currently, 41.4% of Alabama’s population is fully vaccinated, well below the national average of 54.7%. Experts project that Alabama could again experience a higher rate of deaths than births in 2021, if the state continues down its current path.