COVID-19 Situation Report
EPI UPDATE The WHO COVID-19 Dashboard reports 231.7 million cumulative cases and 4.75 million deaths worldwide as of September 27. Global weekly incidence and mortality continue to decrease for the third consecutive week.

Global Vaccination
The WHO reported 5.92 billion cumulative doses of SARS-CoV-2 vaccines administered globally as of September 27. A total of 3.38 billion individuals have received at least 1 dose, and 2.46 billion are fully vaccinated. Analysis from Our World in Data indicates that the overall trend in global daily vaccinations continues to decline, down to approximately 30 million doses per day*. The global trend continues to closely follow Asia. Our World in Data estimates that there are 3.52 billion vaccinated individuals worldwide (1+ dose; 44.7% of the global population) and 2.59 billion who are fully vaccinated (32.9% 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.

As we observed previously with 1+ dose coverage, Oceania’s full vaccination coverage (30.8%) is quickly approaching the global average (32.9%). Oceania could surpass this benchmark in the next several days, which would leave Africa (4.2%) as the only continent below the global average. Oceania and Africa were reporting similar full vaccination coverage as recently as late May, but vaccination efforts in Oceania have progressed rapidly over the past several months.

The US CDC reports 42.9 million cumulative COVID-19 cases and 686,639 deaths. Daily incidence continues to decline at the national level, down to approximately 115,000 new cases per day, which would be the lowest average since early August. Daily mortality appears to have leveled off at approximately 1,500 deaths per day.

It appears that daily mortality in Florida has continued to increase since late August, when the state changed its COVID-19 mortality reporting policy. The Florida Department of Health shifted from assigning dates to COVID-19 deaths corresponding to the date they were reported to the date of death. This results in lower reports for recent days due to the inherent reporting lag, which can give a false impression of rapidly declining daily mortality. Deaths are then filled in retrospectively on the date of death as they are reported to the state, which can take days or weeks after the death occurs. At the time of the change, we estimated that Florida’s daily mortality was likely greater than 200 deaths per day. Since then, the average increased to at least 363 (September 1), and it has remained greater than 200 from at least August 7 through September 15. Florida’s daily incidence plateaued from approximately August 10-30 before decreasing. If historical trends continue, we can expect to observe a corresponding decrease in daily mortality around this time; however, it could be another several weeks before Florida’s mortality reporting fills in enough for that trend to be evident.

US Vaccination
The US has administered 391 million cumulative doses of SARS-CoV-2 vaccines. The daily vaccination trend continues to decline from the most recent peak on August 29* (approximately 850,000), down to fewer than 600,000 doses per day. There are 213.7 million individuals who have received at least 1 dose, equivalent to 64.4% of the entire US population. Among adults, 77.1% have received at least 1 dose, as well as 14.6 million adolescents aged 12-17 years. A total of 183.9 million individuals are fully vaccinated, which corresponds to 55.4% of the total population. Approximately 66.6% of adults are fully vaccinated, as well as 11.8 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.

NOVAVAX WHO EMERGENCY USE LISTING APPLICATION On September 23, Novavax announced its submission to the WHO for Emergency Use Listing (EUL) for its SARS-CoV-2 vaccine candidate. This submission was made in partnership with the Serum Institute of India, which will manufacture the vaccine. Novavax is prioritizing access to low- and middle-income countries (LMICs), and it has already submitted regulatory documents to several individual countries including India, the Philippines, and Indonesia. Novavax and the Serum Institute have jointly pledged to provide more than 1.1 billion doses to the COVAX facility, which also targets LMICs. Phase 3 clinical trials are still ongoing in several countries, including Mexico, the UK, and the US, and preliminary analysis estimates strong efficacy against the original strain of the virus as well as multiple variants of concern (VOCs).  

PFIZER-BIONTECH SUBMIT PEDIATRIC PHASE 2/3 DATA Pfizer and BioNTech announced today that they submitted preliminary data from Phase 2/3 clinical trials on pediatric use of their SARS-CoV-2 vaccine to the US FDA. The submission includes data from nearly 2,300 participants ranging from age 5 years to less than 12 years, and the trial tested a regimen of 2 doses of 10μg each—compared to 30μg for the adult formulation. According to a press release from Pfizer, “the vaccine demonstrated a favorable safety profile and elicited robust neutralizing antibody responses” that were comparable to individuals aged 16-25 years. The companies intend to apply for Emergency Use Authorization (EUA)—as and submit applications to the European Medicines Agency and other national regulatory agencies—for this age group in the coming weeks. White House Chief Medical Advisor Dr. Anthony Fauci indicated that vaccinations for this age group could potentially begin before the end of October. The full trial data have not yet been published publicly or subjected to peer review. Phase 2/3 clinical trials are ongoing for younger children—2 years to less than 5 years and 6 months to less than 2 years—who received 2 doses of 3μg each.

PRIOR INFECTION & IMMUNE PROTECTION As we have discussed previously, protection conferred by vaccination has been demonstrated to be better than protection conferred via natural SARS-CoV-2 infection. Two recent studies, however, provide further analysis of the immune response during and following SARS-CoV-2 infection, including possible protection against re-infection. A study from Japan, published in the Journal of Medical Virology, analyzed the IgG and IgM responses against 2 SARS-CoV-2 proteins (N and S1) in 231 COVID-19 patients. The researchers found that mild cases exhibited stronger immune responses (IgM and IgG) against both proteins early after symptom onset than severe or critical cases. As the disease progressed, the IgM and IgG responses increased in severe and critical cases higher and more rapidly than for mild cases. Additionally, the immune responses remained elevated for longer periods of time in patients with severe or critical disease, while they declined more rapidly for patients with mild disease. ELISA analysis demonstrated that a significantly higher proportion of severe and critical patients remained seropositive at 22 days after symptom onset than for mild patients for the S1 protein but not the N protein. The researchers note that lower immune response among mild cases could potentially signal lower levels of neutralizing antibodies and a shorter period of conferred immune protection against re-infection. Further analysis is needed to better characterize the duration and strength of protection, including the role of the innate immune response and memory B and T cells, and any association with disease severity during the initial infection.

A study in rhesus macaques, published in Science Translational Medicine, evaluated the immune response to re-infection with the Alpha and Beta variants of concern (VOCs) following infection with the original strain of SARS-CoV-2. Researchers infected 18 rhesus macaques with the original strain of the virus (WA1/2020) and then exposed them to either the original strain (control), the Alpha variant, or the Beta variant 35 days later. The animals re-infected with the Alpha variant did not exhibit a notable difference in the concentration of breakthrough virus compared to the control group, whereas the animals re-infected with the Beta variant exhibited much higher concentrations of breakthrough virus. Three (3) additional naïve animals were exposed a single time to the Beta variant in order to compare the immune responses to an original infection and a re-infection. Notably, the animals that were re-infected exhibited lower concentrations of virus, and the re-infected animals exhibited increased neutralizing antibody levels after the second infection, compared to the first. These results suggest a boosted immune response conferred by the initial infection. Interestingly, the animals re-infected with the original strain or the Alpha variant exhibited lower neutralizing antibody responses against the Beta variant, whereas the animals re-infected with the Beta variant generated similar neutralizing antibody responses for all 3 variants. This illustrates that natural infection with one variant can provide some, although not complete, protection against re-infection with other variants, including VOCs; however, the degree of protection could be dependent on the strain or variant. The Delta variant, which has become the dominant strain in many countries, was not evaluated in this study, and as we have covered previously, animal models do not always accurately reflect the immune response in humans.

PANDEMIC ORIGINS Origins of the SARS-CoV-2 virus have been at the forefront of international debate since the onset of the COVID-19 pandemic. The WHO’s Scientific Advisory Group on the Origins of Novel Pathogens (SAGO) was created in May 2020 to identify novel pathogens and advise the WHO on technical and scientific considerations regarding their emergence and re-emergence. SAGO recently released a call for international experts to join the group, with an emphasis on increasing global representation and coordination in the effort to identify the origins of SARS-CoV-2. Some studies have linked SARS-CoV-2 virus to other endemic human coronaviruses and identified genetic similarities between SARS-CoV-2 and other coronaviruses. International debate around the origins of SARS-CoV-2 continues, however, with some experts advocating for a revival of scientific investigations in China and elsewhere, to provide additional information regarding various origin scenarios, including zoonotic transmission or laboratory research. Leading WHO infectious disease epidemiologist Dr. Maria Van Kerkhove emphasized that SAGO is not a new fact-finding mission to China. Rather, SAGO advises the WHO on a framework of study to understand the origins of emerging and re-emerging pathogens, and any future missions, to China or elsewhere, will be coordinated directly between the WHO and national governments.

JAPAN EASING COVID-19 RESTRICTIONS Japanese Prime Minister Yoshihide Suga announced yesterday that Japan will lift its nationwide COVID-19 state of emergency on September 30 and begin relax associated restrictions. While Japan will lift many COVID-19 protective measures, it will reportedly implement testing and vaccine passport programs to mitigate risk while facilitating increased social and economic activity. Local governments may continue to recommend voluntary restrictions on businesses, such as reduced hours of operation and alcohol sales at bars and restaurants, after the emergency is lifted. Japan faced a surge in COVID-19 incidence that coincided with the 2020 Summer Olympic and Paralympic Games, but it has receded rapidly in recent weeks.

AFRICA VACCINE HESITANCY In addition to barriers to accessing sufficient SARS-CoV-2 vaccine supply, African countries are also facing challenges with vaccine hesitancy. Dr. John Nkengasong, Director of the Africa CDC, recently commented on a potential link between international travel restrictions in the UK and hesitancy among African populations. The concern stems from the limited list of countries for which travelers arriving in the UK can “qualify as fully vaccinated.” Travelers vaccinated under a UK, EU, or US vaccination program or individuals arriving from a list of 18 countries who can show proof of full vaccination can enter the UK as “fully vaccinated” travelers, with limited restrictions or quarantine or testing requirements. Notably, the list does not include any countries from Africa, which Dr. Nkengasong argues could serve as a disincentive to get vaccinated. If travelers from African countries cannot qualify as fully vaccinated, even with documentation of full vaccination, some individuals may not see value in the vaccination. Similar opposition has been reported in India and other parts of Asia as well as Latin America. Dr Richard Mihigo, an official from the WHO's Africa region, called on countries to develop a cohesive global system for demonstrating vaccination status and lift travel restrictions for vaccinated travelers that are dependent on country.

SOUTHEAST ASIA ECONOMIC IMPACT The COVID-19 pandemic and associated restrictions continue to have long-term negative effects on local, national, and global economies. In Southeast Asia, several major economic forecasts have downgraded their previous projections and warn of slower economic growth in 2021. The Asian Development Bank lowered its previous regional projection from 4.4% to 3.1% growth over the course of 2021, which signals slower economic recovery from the pandemic. Additionally, the bank lowered its growth projections for all national-level economies, with the exception of the Philippines and Singapore, and Singapore is now the only country in Southeast Asia projected to grow its economy by more than 5% in 2021.

Similarly, the World Bank downgraded its economic growth projections for “developing countries in East Asia.” The new 2021 projection for these countries falls from 4.4% growth to just 2.5%, which stands in stark contrast to the projected 8.5% growth in China. Even in countries that are currently exhibiting stronger economic growth, the trend is slowing as COVID-19 surges continue, driven largely by the Delta variant. The report emphasizes that the pandemic is compounding growing inequality in the region, which will have negative impacts on future economic growth.

Following COVID-19 surges tied to Delta variant, some Southeast Asian countries are once again opening borders to allow travel and tourism, including to some population island destinations in the region. Countries are implementing combinations of vaccine mandates and testing requirements in order to allow international travelers to arrive without lengthy quarantines. Some national and local economies rely heavily on tourism to drive their economies, and they have been severely impacted by travel restrictions during the pandemic. Some countries are moving slowly, with initial limits on traveler volume for specific destinations (including some local areas with high vaccination coverage), before expanding. Some countries that limited domestic travel during the pandemic (eg, to remote islands) are also resuming some domestic travel and tourism opportunities.

NEW YORK HEALTHCARE WORKERS The New York Governor Kathy Hochul, signed an executive order on September 27 to address potential worker shortages as the state’s vaccine mandate goes into effect. The executive order allows the Governor to activate the National Guard or bring in healthcare workers from other states to fill critical personnel shortages. Early evidence indicates that thousands of previously unvaccinated healthcare workers showed up to vaccination sites to receive their first dose in the hours before the mandate went into effect. Approximately 5,000 employees remain unvaccinated, which is a sharp decline from 8,000 a week ago. The statewide vaccination coverage for hospital employees is now reported as 92% with at least 1 dose, and the vaccination also increased among nursing home employees, up from 84%to 92%. Despite these encouraging signs, some hospital employees are still threatening to accept being fired rather than get vaccinated. Some of these individuals indicated that they feel betrayed by the hospital system and government, and they do not trust the vaccine, despite widespread evidence of safety and efficacy. Employees who remain unvaccinated could be put on unpaid leave and eventually fired. The CEO of the New York City Health+Hospitals health system reported that all facilities are currently functional and that there are no serious reports of staffing shortages. 

US SCHOOL TESTING Inconsistent SARS-CoV-2 testing procedures and requirements at schools across the US are raising concerns with parents and stressing the capacity of the school systems trying to implement them. Even school districts in the same city can have very different testing and isolation standards. In Texas, for example, the San Antonio Independent School District offers weekly testing for all students and staff, which consumes a lot of time and resources, even though only 30% of students are participating in the program. Conversely, nearby Boerne Independent School District offers testing only by appointment, and symptomatic students and staff are not referred for testing or sent home unless they can no longer participate in classroom instruction.

While some school districts are foregoing robust testing programs based on the belief that they are unnecessary, others are unable to implement them due to a lack of resources, including access to test kits and personnel to conduct large numbers of regular tests. In Illinois, the state reported surge of enrollments in its statewide school-based testing program as daily incidence increased across the state and the new school year approached. But because schools enrolled late in the process, most do not yet have the logistics and operational systems in place to implement the testing programs. It can take 3-6 weeks to establish these systems, which has delayed testing in some schools, even after classes have already resumed. The Berkeley (California) Unified School District used state COVID-19 funding as well as its own budget to hire 21 personnel, just to implement its testing program; however, most school districts do not have the funding available to hire new, dedicated staff for testing programs.

US RAPID TEST SHORTAGE A nationwide shortage of SARS-CoV-2 rapid antigen tests has been reported in the US, while capacity for PCR-based tests remains high. PCR tests must be processed by a lab, however, and results can often take between 1-3 days (or longer). Rapid tests and at-home tests may have a slightly lower accuracy than PCR tests, but they can still identify nearly 98% of infectious cases and provide convenient results within 15-20 minutes. The shortage of rapid testing kits means that schools, nursing homes, shelters, and workers that rely on fast testing results to go to work each day or prevent outbreaks among at-risk populations are struggling to access adequate resources. Increased wait times for testing results mean that shelters, clinics, and schools are at increased risk for outbreaks, and workers who require daily testing could be forced to miss work and lose income. 

The nationwide shortage of rapid tests may be a function of decreased testing demands and increasing vaccination coverage over the summer. The Delta variant surge and slowing vaccination progress are driving increased demand for rapid tests, and manufacturers have not yet increased production capacity to catch up. Insufficient supply of rapid and at-home tests is driving up testing demand at other locations, including urgent care centers.

The increased demand and supply limitations for rapid tests is driving up the prices of some other testing products. The CARES Act passed in 2020 requires that insurers pay the cost of SARS-CoV-2 testing conducted at out-of-network laboratories. One company, GS Labs, is routinely charging US$380 per test, and insurers argue that the high cost is “price-gouging,” and in some instances, they are refusing the pay. The elevated cost of these tests could result in higher insurance premiums. GS Labs argues that it approached insurers about becoming an in-network provider for reduced costs, but it was generally rejected. The company also cites its excellent service and a high start-up cost as justification for the elevated price for its tests. A representative for the company emphasizes that customers can schedule an appointment for immediate testing and receive results within 15-20 minutes, while many drugstores and pharmacies have no rapid tests available. There are currently several ongoing lawsuits that aim to determine how much insurers have to pay. Increasing the availability of rapid and at-home tests, which typically cost on the order of US$20, would help increase testing access and reduce the need for higher-cost testing options.