COVID-19 Situation Report
Applications Now Open for Johns Hopkins Center for Health Security Educational Opportunities for 2022-2023 Academic Year
In a world of rapid innovation in the biological sciences, the emergence of new diseases, and changing environmental pressures, health security risks to the global community are a rising concern. The field of health security has a growing need for trained expertise that can provide science-based solutions and inform global policies to shape preparedness and response efforts. The Johns Hopkins Center for Health Security is pleased to announce it is now accepting applications for its educational opportunities for the 2022-2023 academic year. The Johns Hopkins Center for Health Security provides 2 Masters of Public Health scholarships and funds 2 PhD candidates for the Health Security PhD track at the Johns Hopkins Bloomberg School of Public Health.
These funding opportunities are supported by Open Philanthropy and are targeted toward students with an interest in the field of health security, particularly in pandemics and global catastrophic biological risks.
EPI UPDATE The WHO COVID-19 Dashboard reports 212.4 million cumulative cases and 4.44 million deaths worldwide as of August 24. The global weekly incidence increased for the ninth consecutive week, up 1.1% over the previous week. The trend continues to taper off toward a peak or plateau. Over the past several weeks, weekly incidence has decreased in Africa and South East Asia, held relatively steady or peaked in the Eastern Mediterranean region and Europe, and increased steadily or exponentially in the Americas and the Western Pacific region. Global weekly mortality increased for the seventh consecutive week*, up 1.8% compared to the previous week. If the global mortality continues on this trajectory, the cumulative total could surpass 4.5 million deaths in the next week.
*With the exception of the week of July 19, when Ecuador reported 8,786 deaths.

Global Vaccination
The WHO reported 4.62 billion cumulative doses of SARS-CoV-2 vaccines administered globally as of August 23. The WHO reports that a total of 1.80 billion individuals have received at least 1 dose, and 1.06 billion are fully vaccinated. Analysis from Our World in Data indicates that the global daily doses administered is decreasing steadily from its second-highest peak, down from 42.7 million doses per day on August 4 to 35.8 million*. The global trend continues to closely follow the trend in Asia. Our World in Data estimates that there are 2.55 billion vaccinated individuals worldwide (1+ dose; 32.7% of the global population) and 1.92 billion who are fully vaccinated (24.6% of the global population). We expect the global total to surpass one-third of the population with 1+ dose and one-quarter with full vaccination in the next week.
*The average doses administered may exhibit a sharp decrease for the most recent data, 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 reported 37.8 million cumulative COVID-19 cases and 626,833 deaths. Daily incidence continues to increase, surpassing 140,000 new cases per day, the highest average since January 30. After reaching a low of 11,653 new cases per day on June 18, the current surge is more than 50% of the way back to the United States’ highest peak—254,111 on January 10. Daily incidence continues to taper off, however, and if the trend continues on this trajectory, we expect the surge to peak in the next several weeks. Daily mortality continues to increase as well, up to 745 deaths per day, the highest average since March 22*. The current average is now higher than it was during the lull between the summer 2020 and winter 2020 surges.
*Changes in the frequency of 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 averages reported here may not correspond to the most recent dates.

US Vaccination
The US has administered 363.3 million cumulative doses of SARS-CoV-2 vaccines. Daily vaccinations continue to increase slowly, up to more than 730,000 doses per day*. Now that the US FDA has issued full approval for the Pfizer-BioNTech vaccine, we will monitor vaccination trends closely to see if there is any associated increase in vaccinations. On August 17, the US surpassed 200 million cumulative vaccinated individuals (1+ dose). The total is now up to 201.7 million, equivalent to 60.8% of the entire US population. Among adults, 73.1% have received at least 1 dose, as well as 12.9 million adolescents aged 12-17 years. The US also surpassed 50 million vaccinated (1+ dose) adults aged 65 years and older, equivalent to 91.4% of that age group. A total of 171.1 million individuals are fully vaccinated, which corresponds to 51.5% of the total population. Approximately 62.5% of adults are fully vaccinated, as well as 9.7 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 APPROVAL FOR PFIZER-BIONTECH VACCINE The US FDA on August 23 granted full approval to Pfizer-BioNTech’s 2-dose SARS-CoV-2 vaccine, which will be marketed as Comirnaty, for the prevention of COVID-19 disease among individuals aged 16 and older. The US regulator’s approval of the vaccine places it on par with other marketed vaccines, possibly reassuring some who have been hesitant to receive the shots, and opens the door for employers and other entities to mandate vaccination. In a statement, FDA Acting Commissioner Dr. Janet Woodcock said the vaccine, the first for SARS-CoV-2 to receive full regulatory approval, “meets the high standards for safety, effectiveness, and manufacturing quality the FDA requires of an approved product.” Notably, the FDA’s approval came only 97 days after Pfizer-BioNTech finished filing its 360,000-page biologic license application, about two-fifths the usual time for such an evaluation. Despite the speedy approval, the agency assured that it kept with its “existing high standards for vaccines in the US.” Regulators are reviewing Moderna’s application for full approval of its SARS-CoV-2 vaccine, and J&J-Janssen is expected to submit its application soon. 

The Pfizer-BioNTech vaccine will continue to be available under an emergency use authorization for 12- to 15-year-olds until the company files for full approval for that age group. Usually, physicians can prescribe FDA-approved products for “off-label” purposes, for reasons other than their original intent. However, the FDA and the American Academy of Pediatrics warned against such use for children under age 12. Pfizer said it expects results from studies involving younger children, ages 5 to 11, to be available by the end of September. Additionally, the FDA reminded doctors that third, or “booster,” doses of the Pfizer-BioNTech and Moderna vaccines have only been authorized for people with compromised immune systems, not for the general population, and strongly recommended against providing them until agency regulators can review whether they are safe and effective and the CDC makes a recommendation. More than 92 million people in the US have been fully vaccinated using the Pfizer-BioNTech vaccine.

VACCINE MANDATES The US FDA’s approval of the Pfizer-BioNTech SARS-CoV-2 vaccine, which comes amid a fourth pandemic wave fueled by the highly transmissible Delta variant, spurred a string of vaccination requirement announcements by corporations, universities, hospitals, and other organizations. In an address on the vaccine’s approval, US President Joe Biden called on more employers and state and local officials to implement mandates, saying, “Do what I did last month. Require your employees to get vaccinated or face strict requirements.” In late July, President Biden implemented requirements for all federal workers to be vaccinated or face regular testing, social distancing, mask wearing, and limits on official travel. A recent survey from the National Association for Business Economics showed 79% of the group’s members favor vaccine requirements for workers before they return to the workplace, and the US Chamber of Commerce also has expressed its support for vaccine requirements or weekly testing. 

Shortly after the FDA’s announcement on August 23, several entities announced vaccine requirements:
  • The US Department of Defense will mandate SARS-CoV-2 vaccination for all military service members now that a vaccine has full approval, with a timeline to be provided in the coming days.
  • In New York City, Mayor Bill DeBlasio announced all of the city’s public school teachers and staff must be vaccinated with at least one dose by September 27, with no option to choose weekly testing. The decree affects about 148,000 employees, as well as contractors, of the New York City Department of Education. At least 2 large city workers’ groups are expected to file labor complaints or take legal action.
  • In New Jersey, Governor Phil Murphy said all employees of any school in the state, including public and private, will be required to be fully vaccinated by October 18 or be tested once or twice weekly “at a minimum.”
  • Several major US energy companies—including Chevron Corporation, Valero Energy Corporation, Pioneer Natural Resources, Schlumberger, and Hess—announced they will require vaccinations for at least some of their employees, several as a condition of employment.
  • Pharmacy chain CVS Health is requiring its pharmacists to be fully vaccinated by November 30, while all other employees who interact with patients and corporate staff must be vaccinated by October 31.
  • Announcing an agreement with unions representing more than 30,000 employees, Disney World will require workers to get the shots by October 22.
  • The University of Minnesota System announced the SARS-CoV-2 vaccine will be added to its list of mandatory immunizations for its 60,000 students. The Louisiana State University, University of Louisiana and Southern University systems and the State University of New York system all announced vaccines will be mandatory for students after previously saying they would require the shots once the FDA granted final approval.
  • At least 145 hospitals and health systems nationwide will require the shots for their employees now that the Pfizer-BioNTech vaccine is approved.

More mandates are expected, as some say they might be the only way to significantly increase vaccination rates amid continued hesitancy. A recent Kaiser Family Foundation poll showed that 3 out of 10 unvaccinated people indicated they would be more likely to get a vaccine if it were FDA-approved. However, whether full approval spurs the approximately 85 million unvaccinated but eligible US residents to get the shots remains to be seen.

HEALTHCARE WORKER RESILIENCY As the Delta variant drives surges in new COVID-19 cases across the US, the nation’s hospitals are overwhelmed. Some hospitals have reported emergency departments with wait times up to 30 hours, dwindling intensive care unit (ICU) capacity, and unstaffed beds due to staffing shortages. Frontline healthcare workers are facing burnout and frustration over unvaccinated patients, who represent the sickest and most likely to die due to COVID-19. Their perseverance through the 3 previous surges is turning to distress during this fourth wave. However exhausted, hospital staff continue to treat people with COVID-19, but say they are disturbed over the rising number of advanced cases among young people and the unvaccinated. Doctors say this surge could have been avoided if more people were vaccinated and continued following preventive measures such as masking and physically distancing. One infectious disease specialist at the University of North Carolina likened going to work to “watching the same house burn down time and time again.” The mental health harm to healthcare workers who must watch people die who likely would not have had they been vaccinated is difficult to quantify, but the relentless nature of the pandemic will no doubt have long-term impacts on medical care in the US. 

US NURSING SHORTAGE Nursing shortages in the US are not new, but the COVID-19 pandemic has exacerbated the problem, testing the physical and mental health of the nation’s nurses as patients flood emergency departments and fill hospital beds amid a fourth surge of cases driven by the Delta variant. More than a year and a half into the pandemic, myriad nurses have retired, made career shifts, taken higher paying jobs with staffing agencies or hospitals with more resources, or simply walked off the job, increasing staffing shortages and contributing to burnout among all healthcare workers. Nurses also say they are angered that many people—in the general public and among their ranks—refuse to get vaccinated or wear masks. Additionally, more than 1,200 nurses have died of COVID-19. 

The staffing shortages are impacting care not only for COVID-19 patients but also others who need urgent medical care because of increased emergency room wait times, postponed surgeries, and, in some cases, an inability to provide adequate care due to the time and attention needed for COVID-19 patients. According to analysis from The New York Times, 1 in 5 intensive care units nationwide is at 95% capacity, a level at which experts say it is difficult to maintain minimum care standards. Various states across the country—including Georgia, Texas, South Dakota, Arkansas, and South Carolina, among others—have said nursing shortages have worsened during the pandemic. Officials indicate that finding ways to recruit, hire, and keep nurses are the main problems, with some hospitals noting they could increase bed capacity with sufficient nursing staff. Many experts fear the nursing shortage will worsen as the pandemic continues to deepen burnout.

IVERMECTIN WARNING: YOU ARE NOT A HORSE Over the weekend, the US FDA renewed its warning that the anti-parasitic animal drug ivermectin should not be used to treat or prevent SARS-CoV-2 infection in humans. The FDA’s message appeared on Twitter with the statement “You are not a horse. You are not a cow. Seriously, y'all. Stop it.” The tweet linked to the agency’s previous statement posted in March 2021. The reiterated warning came a day after the Mississippi State Department of Health issued an alert warning people against using the drug. Ivermectin is commonly used to prevent heartworm and other parasites in animals, and the drug is FDA-approved to treat humans with intestinal complications caused by parasitic worms and for topical use for conditions such as head lice and rosacea. However, ivermectin is not approved for nor recommended by the FDA to treat or prevent COVID-19. According to internal US CDC data reviewed by ABC News, distribution of the drug during the first week of August increased 19-fold. If used improperly, ivermectin can cause several potentially serious side effects, including seizures, coma, or death.

BREAKTHROUGH INFECTIONS & TRANSMISSIBILITY There have been growing levels of concern and conversation surrounding “breakthrough infections,” which are confirmed SARS-CoV-2-positive cases in fully vaccinated individuals. While these cases are still comparatively rare among the larger COVID-19 case burden, experts and the public alike are worried about implications for vaccinated individuals. Most of the recorded breakthrough cases are linked to the Delta variant of concern, which is currently responsible for nearly all new cases in the United States. Encouragingly, a small percentage of breakthrough cases have resulted in severe manifestations of COVID-19 that needed hospitalization. 

While the primary objective of vaccination—preventing severe COVID-19 or death—seems to be holding against the Delta variant, the secondary goal of preventing person-to-person transmission may not be as strong against Delta infections as for other variants or wild-type SARS-CoV-2. Some preliminary studies have found that vaccinated individuals with breakthrough infections can exhibit similar viral loads (measured in PCR Ct values) as those in infected unvaccinated individuals. While higher viral loads can be correlated with the amount of virus shed during normal person-to-person interactions, another preprint study found that high viral load did not necessarily result in shed infectious viral particles. More research is needed to understand the risk of transmission from breakthrough cases to both vaccinated and unvaccinated persons and to understand the viral dynamics in the immune systems of vaccinated individuals. Experts maintain that, given the current evidence, vaccination remains the best tool in defeating SARS-CoV-2 and the Delta variant surge. 

SARS-COV-2 HOUSEHOLD TRANSMISSION A study published last week in the Journal of the American Medical Association (JAMA) found that younger children are more likely to transmit SARS-CoV-2 to other household members than older adolescents. Between June 1 and December 31, 2020, researchers in Ontario, Canada, conducted a population-based cohort study involving 6,280 households that had one index case of confirmed SARS-CoV-2 infection in a member younger than 18 years old. The mean age of the children with COVID-19 was 10.7 years, and 45.6% were female. Of the total households, secondary transmission occurred in 27.3% of households. According to the researchers, children aged 0 to 3 years had the highest odds of transmitting SARS-CoV-2 to other household members when compared with older children aged 14 to 17 years (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.17-1.75). Additionally, children aged 4 to 8 years and 9 to 13 years also had increased odds of transmission when compared with older children (aged 4-8 years: OR, 1.40; 95% CI, 1.18-1.67; aged 9-13 years: OR, 1.13; 95% CI, 0.97-1.32).

Household settings may aid SARS-CoV-2 transmission due to poor or limited ventilation, shared spaces or materials, and frequent close contact with household members. Additionally, it is often challenging to implement non-pharmaceutical interventions such as physical distancing or mask wearing within homes. Experts note that children are more likely to be underdiagnosed for COVID-19 because many have asymptomatic or mildly symptomatic cases. As children return to school amid a surge driven by the highly transmissible Delta variant, parents are concerned about the potential for household transmission. The study’s findings have implications for infection prevention within households, schools, and daycares, especially those with infants and toddlers who appear to have the highest infectivity. The researchers note that further research is required to determine the differences in viral shedding and presentation of symptoms among age groups in order to better prevent secondary transmission in these settings. In an editorial in the same JAMA issue, scientists from the University of Pennsylvania said vaccination for eligible household members should help alleviate fears of SARS-CoV-2 secondary transmission from infected children.

FLORIDA OXYGEN SHORTAGE Florida’s COVID-19 surge appears to have peaked over the past week in terms of daily incidence, but increasing new hospitalizations and current hospitalizations are placing a major burden on hospital and health system operations, particularly in severely affected areas. On August 20, the Orlando Utilities Commission (OUC) and Orlando Mayor Buddy Dyer requested that customers limit water use, particularly for watering lawns and washing cars, in order to conserve liquid oxygen to support local health systems’ COVID-19 responses. Liquid oxygen is used to treat the city’s potable water—”to remove the slight discoloration and rotten-egg smell that is found naturally in Florida's water supply”—and OUC typically consumes 10 trucks of liquid oxygen per week. The company is aiming to reduce its liquid oxygen consumption by 25-50% in order to divert the remainder to hospitals that are struggling to meet the demand due to the COVID-19 patient surge. As we covered previously, high-flow oxygen therapy has emerged as a primary clinical treatment option for severe COVID-19 patients, and hospitals, cities, and countries have faced major challenges securing sufficient oxygen supply during major surges. The OUC request indicates that customers should expect the conservation efforts to last at least 2 weeks.

AVERTED DEATHS Researchers from Indiana University (US) and the RAND Corporation published findings from their analysis on the impact of early SARS-CoV-2 vaccinations in the US. The study, published in Health Affairs, included data on state-level weekly vaccination rates and COVID-19 mortality during the first 5 months that SARS-CoV-2 vaccines were available to the public. The researchers developed a series of multivariate regression models to identify any associated effects on COVID-19 mortality that accounted for state-level variations in state policies and environments as well as the anticipated lag between vaccine administration and any effects on mortality.

The researchers observed a significant association between higher vaccination rates and decreasing mortality across all states, although the magnitude of the benefit varied from state to state. On average, states exhibited a decrease in the expected COVID-19 mortality of 5 deaths per 100,000 population, equivalent to nearly 140,000 averted deaths nationally over the study period. At the state level, the decreased mortality ranged from Hawai’i with 1.1 fewer deaths per 100k to New York with 11.7. Not surprisingly, the effect of vaccination increased over time, as individuals received their second doses and developed the full protective immune response. The impact of vaccination began to increase noticeably starting in early-to-mid February. Notably, vaccine availability was limited to priority populations during most of the period from December 2020-May 2021; however, this period does cover the majority of the initial wave of vaccinations in the US.

ORIGINS OF NOVEL PATHOGENS The WHO on August 20 issued a call for experts to join its new Scientific Advisory Group for the Origins of Novel Pathogens (SAGO), which will advise the UN health agency on technical and scientific considerations regarding the origins of emerging and re-emerging pathogens capable of causing epidemics or pandemics. The group also will guide the WHO on next steps for investigating the origins of SARS-CoV-2. The multidisciplinary effort is an attempt to depoliticize future investigations into disease origins by creating a global framework for conducting scientific-based studies and data-driven efforts to better predict, detect, prevent, and respond to future outbreaks. SAGO, which will include 25 experts from various fields and with different technical skills, is expected to hold its first meeting virtually in late September or early October.

BOTSWANA VACCINATION With 52 African countries rolling out SARS-CoV-2 vaccination campaigns, lessons from the challenges and successes in each country will help other nations learn about how to implement their own vaccine rollouts. Botswana, along with 3 other African nations, has completed an intra-action review (IAR) of its early vaccine rollout with support from the WHO. According to Dr. Malebogo Kebabonye, Director of Health Services at the country’s Ministry of Health and Wellness, having a National Vaccine Deployment Plan with multi-sectoral involvement and coordination in place before receiving the first shipment of vaccines helped communities take ownership and improve acceptance of vaccines. Additionally, solid financing and monitoring and evaluation tools helped strengthen Botswana’s initial vaccine rollout. However, Dr. Kebabonye noted that tightening supplies of SARS-CoV-2 vaccines and healthcare worker shortages contributed to increased distrust about the rollout, with misinformation spread on- and offline. She urged other countries to take incremental and agile approaches to vaccine rollouts, with emphasis on testing and learning. Chanda Chikwanda, Lead of WHO Africa’s Vaccines Learning Agenda, urged other countries in the region to plan for multiple scenarios and conduct IARs. Nine (9) other African countries have expressed interest in completing IARs.

VARIANT VACCINE The Coalition for Epidemic Preparedness Innovations (CEPI) last week announced it will provide up to US$20.6 million to Gritstone bio, Inc. to support the development of a “next-generation” SARS-CoV-2 vaccine. The funding—part of CEPI’s larger portfolio supporting next-generation vaccine development—will be used for a Phase 1 clinical trial of a self-amplifying mRNA vaccine candidate. A self-amplifying approach could provide a single-shot, low-dose vaccine that would elicit immune responses to specific antigens. As new SARS-CoV-2 variants emerge, novel antigens could be rapidly switched out in the vaccine, so variant-specific versions could be ready for production in about 1 month. Gritstone’s vaccine candidate might also produce T-cell immune responses against non-spike protein gene fragments, which potentially could provide more broad protection against various SARS-CoV-2 strains.

DNA VACCINE India’s drug regulator last week granted emergency use approval for the world’s first DNA platform SARS-CoV-2 vaccine for people ages 12 and older. Zydus Cadila’s 3-dose ZyCoV-D vaccine uses a piece of genetic material from the SARS-CoV-2 virus to help the body’s immune system recognize and respond to the virus if exposed. The company claims the vaccine has 66.6% efficacy against symptomatic COVID-19, but no safety, immunogenicity, nor efficacy data supporting the claims are available publicly, either published or preprint. This is the second time the Indian government has authorized a domestically produced vaccine without Phase 3 trial data. The first was Bharat Biotech’s Covaxin, authorized in January 2021. Some experts called on the company and the Indian government to provide more publicly available data to improve transparency.