COVID-19 Situation Report
EPI UPDATE The cumulative global COVID-19 incidence surpassed 200 million cases:
1 case to 25 million: 239 days
25 million to 50 million: 69 days
50 million to 75 million: 42 days
75 million to 100 million: 39 days
100 million to 125 million: 58 days
125 million to 150 million: 36 days
150 million to 175 million: 43 days
175 million to 200 million: 53 days

The WHO COVID-19 Dashboard reports 200.8 million cumulative cases and 4.26 million deaths worldwide as of 12:00pm EDT on August 6.

Global Vaccination
The WHO reported 3.98 billion doses of SARS-CoV-2 vaccines administered globally as of August 5. The WHO reports a total of 1.56 billion individuals have received at least 1 dose, and 781 million are fully vaccinated. Analysis from Our World in Data shows that the global daily doses administered approached the record high on August 4, with 43.0 million doses per day*. The global trend continues to closely follow the trend in Asia. Our World in Data estimates that there are 2.30 billion vaccinated individuals worldwide (1+ dose; 29.6% of the global population) and 1.18 billion who are fully vaccinated (15.2% of the global population).
*Over the past several weeks, we have observed a pattern of a sharp decrease in the average doses administered for the most current day. This decrease eventually disappears, which indicates that it is an artifact of reporting. Moving forward, we will attempt to capture the longer-term trends, which may not necessarily align with the most recent update.

The US CDC reported 35.4 million cumulative COVID-19 cases and 611,958 deaths. Despite considerable vaccination coverage at the national level, daily incidence continues to accelerate, mirroring the early stages of previous surges. Daily incidence is now up to nearly 90,000 new cases per day, the highest average since February 13. Daily mortality also continues to increase, up to 377 deaths per day, which is more than double the most recent low on July 10 (174)*. It appears that daily mortality may be starting to increase exponentially, but additional data are needed to more fully characterize the longer-term trend.
*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 current date.

As the current US surge continues, COVID-19 hospitalizations are increasing nationwide. New hospital admissions per day are the highest since February 14 and more than 4 times the most recent low in late June. Several states are setting new records and still increasing, and several others are approaching their current record. Florida is currently reporting 40% higher than its previous highest peak, and Louisiana is reporting 8% higher than its previous record. Numerous states in HHS Region 4 (Southeast) are exhibiting concerning trends in new hospitalizations. In fact, the region as a whole is reporting nearly 80% of its highest peak and increasing rapidly. Nationally, new hospital admissions among children (17 years and younger) are only 13% below the record set in early January and increasing rapidly. Notably, Florida’s new hospitalizations among children are nearly double its previous highest peak in January. Arkansas, Kansas, Maine, Mississippi, Missouri, and Texas also are setting new records for new pediatric hospitalizations, which is particularly concerning as some states begin their school year with in-person learning.

Current COVID-19 hospitalizations also are increasing steadily. The number of currently hospitalized patients has more than tripled from slightly more than 12,000 in late June to nearly 45,000, over only 5 weeks. Similar to new hospitalizations, several states are reporting record high totals, particularly in Region 4. Florida is reporting more than 9,500 hospitalized COVID-19 patients, which is 14% higher than any other day with available CDC data. The earliest data are from August 1, 2020, and Florida’s trend at that time was declining, so it is unclear what the actual peak was during that surge. Louisiana is currently only 4% below its highest peak in January 2021. The current surge is increasing rapidly—much more quickly than in the previous surge—and we expect Louisiana to set a new record in the next several days. As a whole, Region 4 is reporting 65% of its highest peak and increasing rapidly. Hawai’i also is exhibiting a rapid increase in hospitalized COVID-19 patients. It is currently equal to its January 2021 peak, and while it is still 34% lower than its highest peak from August 2020, its trend is accelerating rapidly.

Analysis by The New York Times indicates that every state except Rhode Island is reporting increasing current hospitalizations over the past 2 weeks. Notably, Rhode Island’s COVID-19 hospitalizations have decreased steadily since mid-December 2020. Among the states with increasing trends, 10 have more than doubled over the past 2 weeks, including Alabama (+162%), Louisiana (+156%), and South Carolina (+156%), which have increased by more than 150% over that period. Notably, 6 of the 8 states in Region 4 are reporting biweekly increases greater than 100%. The exceptions are Tennessee and North Carolina, which are reporting +87% and +89%, respectively.

US Vaccination
The US has administered 349 million cumulative doses of SARS-CoV-2 vaccines. Daily vaccinations are increasing slowly, now up to 582,867 doses per day*. A total of 193.2 million individuals in the US have received at least 1 dose, equivalent to 58.2% of the entire US population. Among adults, 70.4% have received at least 1 dose, as well as 11.3 million adolescents aged 12-17 years. A total of 165.6 million individuals are fully vaccinated, which corresponds to 49.9% of the total population. Approximately 60.8% of adults are fully vaccinated, as well as 8.6 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.

PFIZER-BIONTECH VACCINE FULL FDA APPROVAL With the number of new COVID-19 cases surging in the US, the US FDA reportedly has taken an “all-hands-on-deck approach” to reviewing data on Pfizer-BioNTech’s SARS-CoV-2 vaccine, aiming to grant full approval by September 6 or possibly sooner, according to multiple sources familiar with the process. However, some agency and White House officials hope the timetable will be accelerated further, with approval coming as soon as August 15, several sources shared. Speaking at a town hall on July 21, US President Joe Biden said he expects final approval by the fall. Pfizer-BioNTech filed its application for full licensing with the FDA on May 7, and the agency announced the vaccine would undergo priority review on July 16, meaning approval would come no later than January 2022. But it appears the FDA is significantly speeding up that timeline.

Real-world data show that full vaccination dramatically reduces the risk of COVID-19-associated hospitalization or death, but the pace of vaccination has largely stalled in the US, with only about 50% of the total population fully vaccinated and 70% of the adult population having received at least one dose. In an August 4 statement, an FDA spokesperson said the agency’s full approval of SARS-CoV-2 vaccines could engender additional confidence among some people and encourage them to get vaccinated. A June poll by the Kaiser Family Foundation found that 3 in 10 unvaccinated adults said they would be more likely to get vaccinated if one of the vaccines currently being used under emergency use authorization received full approval. Notably, the survey concluded that FDA approval might serve as a proxy for alleviating safety concerns, as many respondents appeared to not understand the regulatory process and two-thirds believed that the vaccines currently available already have full FDA approval or were unsure whether they have full approval. Full licensing of a SARS-CoV-2 vaccine also is expected to spur even more employers to implement vaccine mandates and would provide physicians greater latitude to prescribe additional doses for older adults or people with compromised immune systems.

EMPLOYER VACCINE MANDATES Some of the largest employers in the US recently have announced SARS-CoV-2 vaccination mandates for all or some of their employees amid a surge of COVID-19 cases. The US FDA is expected to fully license the Pfizer-BioNTech vaccine within the next few months, a move that could spark more companies to implement requirements. Tyson Foods, Google, Netflix, Disney, Walmart, Uber, Lyft, Morgan Stanley, The Washington Post, and United Airlines are several of the major companies that are requiring that at least some of their employees be vaccinated, either as a condition of employment or in order to return to corporate office buildings. On August 5, CNN announced it fired 3 employees who violated the company’s policies by returning to the office unvaccinated, one of the first known examples of a major company terminating employment for workers who ignore vaccine mandates. 

Reportedly, the Biden administration is considering withholding federal funds from a variety of institutions, including long-term care facilities and universities, in order to encourage more Americans to get vaccinated. The US Equal Employment Opportunity Commission (EEOC) has issued guidance generally permitting employers to institute vaccination mandates in the workplace as long as reasonable accommodations are offered to those with religious beliefs, disabilities, or other conditions that might prohibit vaccination. On July 6, the US Department of Justice published a memorandum explaining that Section 564 of the Food, Drug, and Cosmetic Act, which authorizes the US FDA to issue emergency use authorization (EUA), does not prohibit public and private entities such as businesses and schools from imposing SARS-CoV-2 vaccine requirements. In essence, the regulation permits employers to implement policies requiring vaccination as a condition of employment even when the vaccine is being used under an EUA. Several states have moved to ban future vaccine mandates. As we previously reported, mandatory vaccination requirements twice have been upheld in federal courts. Undoubtedly, additional legal challenges will emerge as more employers, universities, and other entities require proof of vaccination for employees, contractors, and office guests.

NEW YORK CITY VACCINE MANDATE On August 3, New York City Mayor Bill de Blasio announced the Key to NYC Pass program, which requires vaccination for many activities in the city. Starting August 16 (with the program fully implemented by September 13), the program will require individuals to have received at least 1 dose of a SARS-CoV-2 vaccine for indoor dining, indoor fitness facilities, and indoor entertainment venues (eg, theaters, museums). The effort is similar to restrictions implemented in France, but it appears to be the first large-scale program in the US. Last week, Mayor de Blasio announced a vaccine mandate for city employees, which requires weekly testing for unvaccinated personnel. 

Notably, Key to NYC Pass does not refer to an actual pass or smartphone application, but rather to the mandate itself. Individuals have the option to use the physical vaccination card issued by the US CDC, the state’s Excelsior Pass app, or the city’s NYC COVID Safe app to provide documentation of vaccination status, but questions remain regarding how businesses are expected to verify vaccination status, particularly regarding how to verify the authenticity of vaccination cards. While both apps also document negative test results, these are not considered a valid substitute for vaccination under the city’s mandate.

US EVICTION MORATORIUM Following the expiration of a federal moratorium on evictions on July 31, the US CDC issued a new temporary moratorium on August 3 that targets areas of “substantial or high [SARS-CoV-2] transmission.” Substantial transmission corresponds to counties with more than 50 new weekly cases per 100,000 population and test positivity of 8% or higher over the past week. Based on the CDC’s COVID-19 risk classification, these counties currently account for approximately 90% of the US population. The new order is scheduled to expire on October 3. The moratorium aims to provide additional time for states to distribute rental assistance funding at a time when the increasing prevalence of the Delta variant is increasing the COVID-19 risk across the country. 

As the previous moratorium expired, the White House and the US Congress called on each other to act; however, Congress was unable to agree to a legislative solution, and the White House acknowledged that it did not have the authority to take action. In light of a recent US Supreme Court decision to allow the CDC to extend the previous moratorium through July, in part, due to assurances that it would not be extended further, US President Joe Biden noted that the new moratorium will likely “face obstacles.” In fact, one realtor organization has already filed a lawsuit in federal court, and one local judge has reportedly indicated that he will disregard the order. Even if the moratorium is overturned, President Biden indicated that it could potentially remain in place during the litigation process, which would effectively extend protections for renters.

WHO BOOSTER DOSE MORATORIUM The WHO on August 4 called for a temporary, 2-month moratorium on the administration of “booster,” or third, doses of SARS-CoV-2 vaccines for most people, urging a focus on helping all nations catch up with their vaccination efforts to reach at least 10% of their populations by the end of September. In a briefing, WHO Director-General Dr. Tedros Adhanom Ghebreyesus said, “We cannot—and we should not—accept countries that have already used most of the global supply of vaccines using even more of it, while the world’s most vulnerable people remain unprotected.” Of approximately 4 billion doses administered worldwide, more than 80% have been used in high- or upper-middle-income countries. WHO staff said the science supporting booster doses for the vaccinated general population to enhance immunity is not yet clear, and distinguished those shots from additional doses potentially needed among immunocompromised populations for the development of immunity, which they said should be considered part of the initial series and not a booster. Dr. Tedros called for a moratorium on booster doses through at least the end of September, with the possibility of extension, in order to increase the vaccine supply going to the COVAX facility and encouraged leaders of the Group of 20 countries to make “concrete commitments” to help close the global vaccine gap.

The WHO’s call for a booster moratorium comes as several nations begin or move toward starting such programs. Israel on August 1 began providing third doses to adults over age 60 who are at least 5 months from their second dose, with Prime Minister Naftali Bennett on August 5 warning older Israelis to take extreme caution until they receive the additional shot. In Russia, anyone 6 months post-vaccination can receive an extra dose, and in Hungary, those who are 4 months post-vaccination can get one. Other nations, including Germany, the United Kingdom, and France, are set to roll out additional dose campaigns among various segments of their populations beginning in September. The US FDA is expected to announce a plan for additional doses for all populations by early September, with a plan for immunocompromised individuals possibly coming sooner. Despite the WHO’s calls for a moratorium, most countries appear to be moving ahead with plans for additional doses, claiming they will be able to provide the extra shots and donate millions of doses to low- and middle-income countries. Notably, a WHO internal analysis estimates that if only the 11 wealthier nations planning or expecting to begin additional dose campaigns this year were to provide shots to everyone over age 50, they would use approximately 440 million doses of the already tight global supply. If all high- or upper-middle-income countries began such campaigns, the estimate doubles. With COVAX seeking at least half a billion more vaccine doses to distribute before the year’s end, the onus lies with wealthier countries to fill global vaccination gaps with limited supplies. 

VACCINE DIPLOMACY As the Delta variant spreads worldwide, driving up the number of new COVID-19 cases, the US government is under increasing pressure to provide vaccine doses to countries in need. So far, the US has donated more than 110 million doses and plans to donate at least 500 million more. As part of its efforts to improve global vaccine access, the US Department of State is working to support the development of a network of overseas manufacturers to help grow global SARS-CoV-2 vaccine supplies by several billion doses annually. Gayle Smith, US State Department Coordinator for Global COVID-19 Response and Health Security, said she would like to see US vaccine makers—including Moderna, Pfizer, and J&J—support the establishment of low-cost manufacturing facilities and share technological information with other companies to make vaccines available at lower price points. 

To this end, the US International Development Finance Corporation has offered US$2 billion to vaccine makers as incentives. So far, agreements have been made with companies in India, South Africa, and Senegal, but these are for companies to “fill and finish” vaccine doses by obtaining large batch ingredients, blending the product, and filling and packaging vials for distribution. One of these companies, South Africa-based Aspen Pharmacare, this week announced it will increase its annual production capacity for the J&J-Janssen vaccine from 300 million to 500 million beginning in January 2022. Some advocates are pushing for the US to pressure pharmaceutical companies to share the technical expertise necessary for overseas companies to produce the vaccines themselves. Notably, the US government retains ownership of one of the main patents used in the Moderna vaccine, but it has not yet charged royalties, giving the government leverage over the manufacturer

In an effort to counter criticisms it has not done enough to incentivize large pharmaceutical companies to transfer vital technologies, the US—in partnership with nongovernmental organizations and philanthropies—plans to host a high-level leadership summit during next month’s UN General Assembly meeting, with the goal of rallying the international community to increase its pledges for vaccine and public health resources donations. As the US appears to be stepping up its vaccine diplomacy efforts, so does China. Chinese President Xi Jinping on August 5 announced his country hopes to provide 2 billion doses of SARS-CoV-2 vaccines to other countries this year, and will donate US$100 million to the COVAX facility.

MODERNA VACCINE EFFICACY Moderna this week released final analysis of its Phase 3 COVE study data for fully vaccinated individuals at 6 months follow-up. A corresponding preprint published in medRxiv provides details about the study. The placebo-controlled efficacy trial included nearly 45,000 participants aged 16 and older, and roughly 2,250 participants between the ages of 12 and 15. According to the data, the Moderna vaccine’s efficacy after 6 months was 91% among evaluable participants and irrespective of previous SARS-CoV-2 infection. Vaccine efficacy against severe disease was 97%. In South Africa, where the SARS-CoV-2 Beta variant (B.1.351) was dominant during the study, the vaccine efficacy was 100%. However, the study did not evaluate vaccine efficacy against the now widespread Delta variant, and the company acknowledged that additional research is necessary to fully evaluate the vaccine against new variants. 

NOVAVAX VACCINE CANDIDATE Novavax issued several statements this week regarding progress on its candidate SARS-CoV-2 vaccine. Novavax has been working on its application to the US FDA seeking emergency use authorization (EUA), but it appears the company will not submit the application until the fourth quarter of 2021. Despite the delay in seeking emergency authorization in the US, Novavax also announced encouraging information on the international front. Novavax submitted applications for emergency use authorization to regulatory authorities in India, Indonesia, and the Philippines, and it expects to submit an application for emergency use listing to the WHO later this month. Reportedly, emergency use applications are expected to be submitted to Australia, Canada, and the UK starting in September. Novavax is partnering with the Serum Institute in India to manufacture its vaccine. Additionally, the company finalized an advance purchase agreement with the European Commission for up to 200 million doses of the vaccine, with an initial commitment of 100 million doses with the option to add an additional 100 million in 2023.

Novavax also announced preliminary results from an ongoing clinical trial of its vaccine, specifically regarding the effect of an additional dose of the vaccine. In the Phase 2 study, participants received a third dose of the vaccine 6 months after the initial 2-dose regimen. According to a press release, the researchers observed “a 4.6-fold increase in...antibody titers” following the third dose. Additionally, the participants exhibited a 6-fold increase in antibodies effective against the Delta variant. The preliminary data suggest that older adults—aged 60-84 years—could exhibit greater benefit from a booster dose compared to younger adults. The statement indicates that complete data will be published to a preprint server and submitted for peer review.

POST-EXPOSURE PROPHYLAXIS A study published this week in the New England Journal of Medicine shows that REGEN-COV—a combination of the monoclonal antibodies casirivimab and imdevimab—reduced the risk of symptomatic COVID-19 disease by 81% among people exposed to a household contact with confirmed SARS-CoV-2 infection. The trial included 1,505 participants, with half assigned to receive REGEN-COV and the other half to placebo. The participants’ mean age was 42.9 years, 45.9% were adolescent boys or men, 9.3% identified as Black, and 40.5% identified as Hispanic or Latinx. Overall, a single 1,200 mg subcutaneous injection of REGEN-COV reduced the risk of symptomatic and asymptomatic infections by 66.4% among household contacts. Additionally, the median time to symptom resolution (1.2 weeks vs 3.2 weeks) and duration of high viral load (0.4 weeks vs 1.3 weeks) were shorter among REGEN-COV recipients who developed symptomatic COVID-19 than for placebo recipients who developed symptomatic COVID-19. The study’s findings were used by the US FDA in its recent revision to REGEN-COV’s emergency use authorization (EUA), which expanded emergency use for the drug as post-exposure prophylaxis (PEP) for COVID-19 in high-risk adults and pediatric individuals. REGEN-COV remains authorized for the treatment of mild-to-moderate COVID-19 among adults and pediatric patients who are at high risk for progression to severe COVID-19.

LONG COVID/PASC IN CHILDREN According to a study published in The Lancet Child & Adolescent Health, so-called “long COVID,” or post-acute sequelae of COVID-19 (PASC), is rare among children, with most children fully recovering from SARS-CoV-2 infection after 8 weeks. British researchers aimed to determine illness duration and symptoms among UK school-aged children who reported data, through adult proxies, to the COVID Symptom Study. The researchers included data from 1,734 children aged 5 to 17 years who tested positive for SARS-CoV-2, with case control matches who reported information to the database but who tested negative for the virus. Of these children, the most common symptoms were headache (62.2%) and fatigue (55%) and illness duration lasted approximately 6 days. Only 25 (1.8%) of 1,379 children who tested positive experienced symptoms for at least 56 days, with a significant regression in symptoms within the first 28 days. Notably, the data showed that while only 0.9% of the children who tested negative had symptoms lingering for 28 or more days, this control group had more symptoms (median: 9) during the first 28 days and in the few in whom symptoms persisted beyond 28 days (median: 5). While the study’s findings suggest that long-lasting symptoms are rare among children diagnosed with COVID-19, the researchers emphasized the importance of following any child with prolonged illness, whether from SARS-CoV-2 infection or another illness.

VACCINATION FOR PREGNANT WOMEN On August 3, the UK government initiated a study to determine the most beneficial dose schedule for SARS-CoV-2 vaccination in pregnant women. The study will include 600 pregnant women who will be vaccinated using either the Pfizer-BioNTech or Moderna vaccines. The women will receive the 2 doses of these vaccines either 4-6 weeks apart or 8-12 weeks apart in order to determine the best interval. Researchers will analyze blood specimens from each participant collected over 9 follow-up visits as well as a single blood specimen from the newborn and from breast milk. While pregnant women in the UK, US, and other countries are already being vaccinated, this study aims to provide further insight into the immune response in pregnant women and their newborns.

“DELTA PLUS” VARIANT As the prevalence of the Delta SARS-CoV-2 variant of concern (VOC) continues to increase around the world, there are emerging reports of infections caused by a sub-lineage of the Delta variant that includes an additional mutation. The subvariant is being widely referred to as “Delta Plus”; however, this appears to be an informal designation, as there is not yet a mention of that term on the WHO or US CDC VOC websites. India designated Delta Plus as a VOC in late June. Delta Plus refers to the B.1.617.2.1 (or AY.1) variant—a subset of the Delta variant B.1.617.2—which includes an additional mutation (K417N) to the spike protein that is not present in the original Delta variant. The K417N mutation also is present in the Beta variant, and it is believed to help the virus evade immune response, including reduced susceptibility to some monoclonal antibody treatments. The variant tracker reports more than 450 cases involving the Delta Plus variant across at least 30 countries.

In June, Public Health England was among the first to document the K417N mutation in the Delta variant. Information from the Indian Ministry of Health and Welfare indicates that the Delta Plus variant exhibits “increased transmissibility, stronger binding to receptors of lung cells, [and] potential reduction in monoclonal antibody response.” But while the “plus” seems to imply that the variant is more dangerous, it is not yet clear how much it differs from the main Delta variant. As the pandemic continues, new variants will continue to emerge, which could include further evolution of VOCs that possibly result in increased transmissibility, disease severity, and resistance to treatments or vaccines. Genomic surveillance is critical to rapidly identifying and characterizing these variants before they spread widely.