EPI UPDATE The WHO COVID-19 Dashboard reports 185 million cumulative cases and 4.0 million deaths worldwide as of 4:30am EDT on July 9. On July 8, the global cumulative mortality surpassed 4 million deaths:
1 death to 1 million- 251 days
1 to 2 million- 114 days
2 to 3 million- 89 days
3 to 4 million- 89 days
Global weekly incidence increased for the second consecutive week, up 3.8% from the previous week. Global weekly mortality, however, continues to decrease down to its lowest point since late October 2020—a decrease of 6.5% compared to the previous week.
Analysis by Reuters indicates that 19 countries* are currently reporting a daily incidence that is 90% or greater of their highest peak. While these countries represent nearly all of the WHO regions—with the exception of Europe—they tend to be clustered in smaller regional areas. In the Americas, there are 3 countries in Central America and the Caribbean. Cuba, Honduras, and Guatemala are all currently reporting their record high daily incidence to date. In Africa, Tunisia (at its peak) is the only country in the northern region, but there are 5 countries in sub-Saharan Africa. Liberia, Mozambique, South Africa, and Zimbabwe are all reporting record highs, and Rwanda is at 99% of its record. In the Eastern Mediterranean region, Iraq and Kuwait are both reporting 97% of their record highs. The South-East Asia region accounts for a third of the countries globally that are currently exceeding 90% of their highest peak, stretching from Bangladesh to Indonesia. Bangladesh, Indonesia, Myanmar, Thailand, and Vietnam are all at their highest peak. Additionally, Malaysia is at 92% of its record high, and Cambodia is at 92%. Fiji (at its peak) is the only country in the Western Pacific region.
*In addition to WHO countries, Reuters lists the British Virgin Islands at 91% of its highest peak.
Among these countries, most epidemics are continuing to accelerate. In fact, all 19 countries are reporting positive relative changes over the past 2 weeks, and Liberia (-34%) is the only country reporting a negative trend over the past week. Notably, the daily incidence has more than doubled over the past 2 weeks in nearly half of these countries, including Fiji (+201%), Zimbabwe (+276%), Mozambique (+375%), and Myanmar (+403%). The surges in most of these countries began between mid-May and mid-June, although a few are exhibiting long-term increasing trends. It appears that most of the countries with longer-term increases—including Cambodia, Guatemala, Honduras, Iraq, and Malaysia—reported relative peaks in April or May and then declined slightly before their current surges. A number of these countries were reporting fewer than 100 new cases per day as recently as late June, with some as low as single-digits in the weeks and months prior. But as we have discussed previously, even countries with low daily incidence can be at risk for rapidly accelerating epidemics if transmission is not contained. Currently, Liberia is the only one of these countries reporting fewer than 100 new cases per day, and Cambodia, Fiji, and Rwanda are the only other countries reporting fewer than 1,000.
Global Vaccination
UNITED STATES
The US CDC reported 33.6 million cumulative COVID-19 cases and 603,958 deaths. Daily incidence has increased over the past several weeks, up from a low of 11,281 new cases per day on June 20 to 14,884 on July 7, an increase of 32% over that period—including an increase of 16% over the past week. Daily mortality continues to decline, although it increased slightly on July 7. It is likely that reporting delays over the Independence Day holiday weekend are impacting the incidence and mortality figures; however, some states have transitioned from daily to weekly reporting, so the degree of impact may differ compared to earlier in the pandemic.
The CDC published updated genomic surveillance data, including Nowcast projections for June 20-July 3. In the most current official data, the Delta variant (B.1.617.2) reached 30.4% of new cases for June 6-19. The Delta variant remains #2 behind the Alpha variant (B.1.1.7; 44.2%); however, its relative proportion continues to increase rapidly, tripling from the previous 2-week period (10.1%). In the CDC’s projection, Delta is not only the dominant variant, but it accounts for more than half of all new cases in the June 20-July 3 period (51.7%). The prevalence of the Alpha variant continues to decrease steadily, down from a high of 69.9% for April 25-May 8 to 28.7% in the Nowcast projection. The Gamma variant (P.1) is now beginning to decrease slowly as well, down from a high of 11.1% for May 23-June 5 to 8.9% in the projection period. At the regional level, Delta variant prevalence is projected to exceed 50% in 5 of the 10 HHS regions, including 74.3% in Region 8 (Mountain) and 80.7% in Region 7 (Central).
US Vaccination
The US has administered 332 million cumulative doses of SARS-CoV-2 vaccines, and it is administering approximately 484,000 doses per day. A total of 183 million individuals in the US have received at least 1 dose, equivalent to 55.2% of the entire US population. Among adults, 67.3% have received at least 1 dose as well as 9.4 million adolescents aged 12-17. A total of 158 million individuals are fully vaccinated, which corresponds to 47.7% of the total population. Among adults, 58.5% are fully vaccinated, and 7.2 million adolescents aged 12-17 years are fully vaccinated.
In addition to a study recently published in The Lancet that demonstrated sufficient immune response following mixed doses of the AstraZeneca-Oxford and Pfizer-BioNTech vaccines, 2 German studies (both preprint) reported similar findings. The first study included 340 healthcare workers and found similar immune responses among participants who received 2 doses of the Pfizer-BioNTech vaccine and those who received a prime dose of the AstraZeneca-Oxford vaccine followed by a booster dose of the Pfizer-BioNTech vaccine. The second study included 216 participants who received either 2 doses of the AstraZeneca-Oxford vaccine, 2 doses of the Pfizer-BioNTech or Moderna vaccines, or a prime dose of AstraZeneca-Oxford followed by a booster dose of one of the mRNA vaccines. The immune responses in the heterologous group were similar to those who received 2 doses of the mRNA vaccines and better than those who received 2 doses of the AstraZeneca-Oxford vaccine. While these studies are small and evaluate immune response rather than vaccine efficacy against infection or disease, they do provide further evidence that using an mRNA vaccine as the second dose can stimulate sufficient immune response and potentially even improve on 2 doses of the AstraZeneca-Oxford vaccine.
DELTA VARIANT VACCINE EFFICACY Researchers continue to evaluate how well available SARS-CoV-2 vaccines protect against the Delta variant (B.1.617.2), which is driving outbreaks in both vaccinated and unvaccinated communities in several countries and is now the dominant variant in the US. To date, studies show the most widely used shots offer strong protection against severe disease and hospitalization, although protection may be reduced for infection. On July 5, Israel’s Ministry of Health released results of a study examining the effectiveness of the Pfizer-BioNTech vaccine against all circulating variants, including Delta, for the past month beginning June 6. The ministry noted a “marked decline” in the vaccine’s effectiveness in preventing infection (64%) and symptomatic illness (64%). While this rate is lower than the vaccine’s effectiveness prior to circulation of the Delta variant in Israel (95%), and lower than other studies from Britain (88%), Scotland (79%), and Canada (87%), the Israeli study maintained the vaccine was 93% effective in preventing serious illness and hospitalization. Israeli officials cautioned that the study data are preliminary, based on highly localized outbreaks, and potentially had other methodological weaknesses. A Pfizer spokesperson declined to comment specifically on Israel’s data but confirmed other research shows its vaccine is effective against all variants, including Delta, although at a reduced rate.
Pfizer-BioNTech on July 8 announced it plans to seek authorization in the US and Europe for a third booster dose of its vaccine based on “encouraging data.” However, some experts contend there is no indication for a booster or third dose of an mRNA vaccine, and the US FDA and US CDC published a joint statement saying people who have been fully vaccinated do not need a booster shot at this time. The agencies said they will continue to monitor ongoing studies and are “prepared for booster doses if and when the science demonstrates that they are needed.” Pfizer-BioNTech also announced they plan to begin trials as early as next month of a vaccine targeted specifically at Delta, although it is not clear whether this shot would be intended as a booster or an additional, separate vaccination.
As we previously reported, vaccine efficacy is reduced following 1 dose of mRNA or viral vector vaccine versus the full 2-dose schedule. On July 8, researchers from France published a peer-reviewed report in Nature showing a single shot of a 2-dose vaccine (Pfizer-BioNTech or AstraZeneca-Oxford) “barely” offered protection against the Delta variant. Notably, J&J-Janssen recently announced preliminary data demonstrating its single-shot SARS-CoV-2 vaccine generates a strong immune response against all highly prevalent variants for at least 8 months, including Delta. Little is known about the effectiveness of the Chinese-produced vaccines from Sinopharm and Sinovac Biotech Ltd. against Delta, although the companies say they are studying variants. Research and real-world data consistently show that people who are unvaccinated or not fully vaccinated remain at an increased risk of infection and more severe disease, underlining the importance of fully vaccinating as many people as possible, particularly in the face of Delta and other emerging variants of interest and concern.
CUBAN VACCINES Cuban pharmaceutical company BioCubaFarma announced preliminary efficacy estimates for a second candidate SARS-CoV-2 vaccine. The company issued a press release indicating a regimen of its 2-dose Soberana 02 vaccine plus a booster of Soberana Plus demonstrated 91.2% efficacy against symptomatic COVID-19 over a 56-day period in a Phase 3 clinical trial. According to the press release, the trial was conducted in 8 municipalities in the capital of Havana, but it does not provide further details, including the number of participants. A clinical trial of the same vaccine regimen is already underway in children and adolescents. In June, BioCubaFarma announced that another vaccine candidate, Abdala (also a 3-dose regimen), demonstrated 92.3% efficacy in a Phase 3 trial. To our knowledge, the full trial data have not yet been released publicly nor subjected to peer review, but efficacy estimates greater than 90% would put both of Cuba’s vaccines in the same category as others in wider use around the world, including the Pfizer-BioNTech, Moderna, and Sputnik V vaccines. Cuba has a well-established vaccine development sector, which produces approximately 80% of its vaccines as well as some for export.
VACCINE EFFICACY IN IMMUNOSUPPRESSED POPULATIONS The Coalition for Epidemic Preparedness Innovations (CEPI) announced it will co-fund a study to assess immune response to SARS-CoV-2 vaccines in patients aged 18 or older who are immunocompromised or who take immunosuppressive medications following an organ transplant. CEPI will provide $3.1 million alongside $3.6 million in funding from several Norwegian health organizations, including Oslo University Hospital, which will lead the trial. Large trials of vaccine efficacy in immunosuppressed populations have been limited, despite this subpopulation having an increased risk of developing severe COVID-19. The study aims to recruit at least 6,000 patients and 10,000 healthy participants who have received 2 doses of vaccines that are included in the Norwegian National Corona Immunization Program (currently Pfizer-BioNTech and Moderna). The primary goal of the trial is to assess the level of adaptive immune responses in these populations. Participants in the intervention arm of the study who have low or no immune response to vaccination will be offered a booster dose and monitored. Researchers also plan to evaluate the effect of immunosuppressive medications on immune response to vaccination and associated demographic and immunologic indicators.
VACCINATION & HEART INFLAMMATION The US CDC’s Advisory Committee on Immunization Practices (ACIP) on July 7 published an update on the use of mRNA SARS-CoV-2 vaccines following its review of reports of myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the thin tissue surrounding the heart) among some vaccine recipients. ACIP concluded that the benefits of vaccination (prevention of COVID-19 disease and associated hospitalization and death) outweigh the risks (expected myocarditis after vaccination) in all populations for which vaccination is currently recommended. However, the committee noted the balance of benefits and risks vary by age and sex because myocarditis cases occurred predominantly among males less than 30 years old and the risk of complications from COVID-19 increase with age. For every 1 million second doses of mRNA vaccine administered to males ages 12-29 years, 11,000 COVID-19 cases, 560 hospitalizations, 138 ICU admissions, and 6 deaths due to COVID-19 could be prevented, compared with 39-47 expected myocarditis cases after SARS-CoV-2 vaccination. Among older males aged ≥30 years, the benefits increase, with 15,300 COVID-19 cases, 4,598 hospitalizations, 1,242 ICU admissions, and 700 deaths potentially prevented, compared with 3-4 expected myocarditis cases. The authors note their analysis did not include the possible benefit of preventing longer-term COVID-19 symptoms nor multisystem inflammatory syndrome in children (MIS-C). ACIP emphasized the importance of informing providers and families about the benefits and risks of vaccination, including myocarditis, and monitoring for adverse events following vaccination.
Notably, the American Heart Association (AHA) on the same day published a scientific statement on the diagnosis and management of myocarditis in children in the journal Circulation. Though the statement was developed prior to the COVID-19 pandemic, the recommendations could be useful for healthcare providers in identifying and treating myocarditis/pericarditis among young people following SARS-CoV-2 vaccination or infection, as there currently is no standard treatment for either condition. With no alternatives to mRNA vaccines for adolescents available for the foreseeable future, no deaths or severe outcomes from myocarditis/pericarditis reported at the time of ACIP’s meeting, and about one-third of US COVID-19 cases occurring in people ages 12-29 in May 2021—many unvaccinated—most experts agree with the committee’s conclusion to continue recommending vaccination for all people aged 12 and older. Questions remain about whether reports of myocarditis/pericarditis among younger populations will impact vaccination rates, but many experts point out that potential future risks, posed by the Delta variant (B.1.617.2) or another possibly more virulent strain, should prompt parents to vaccinate their children in order to protect them and those around them.
REDUCING VACCINE DOSE As vaccination efforts continue to scale up in most countries, production capacity is still “woefully inadequate” to meet the global demand. Some experts are beginning to speculate whether reducing the dose volume could increase the number of available doses without sacrificing protection. This concept, referred to as “fractionation,” has been implemented in the past for other vaccines, such as yellow fever, polio, and meningococcal conjugate vaccines. In these instances, existing research provided evidence that smaller doses still provided sufficient protection; however, that is not necessarily the case for SARS-CoV-2 vaccines. Because the vaccines are so new—and research to this point has focused principally on establishing safety and efficacy profiles to support regulatory authorization—the necessary data simply are not available to demonstrate efficacy for smaller doses. Small studies early in the development process compared several dose options against each other, but these largely focused on safety rather than efficacy. There have not yet been dedicated efforts to determine the minimum dose required to provide protection.
There is limited evidence that smaller doses of some existing vaccines could stimulate sufficient immune responses, but not enough to provide robust, reliable efficacy estimates. Additionally, it could be argued that the nature of the pandemic demands different calculus in terms of evaluating benefit. Smaller doses of the vaccine might provide less protection at the individual level, but increasing the number of vaccinated individuals could provide a net benefit at the population level. Beyond the technical questions, implementing fractionation at this point in the pandemic—ie, after many higher-income countries have already vaccinated substantial portions of their respective populations—could pose ethical and political challenges, considering that much of the future supply will be allocated to low- and middle-income countries.
COVID-19 THERAPEUTICS The WHO recently updated its living guideline for the use of COVID-19 therapeutics with a strong recommendation to use interleukin-6 (IL-6) receptor blockers, including both tocilizumab and sarilumab, in patients with severe COVID-19 disease. IL-6 is an inflammatory cytokine that is activated as part of the immune response, but can be over-activated during SARS-CoV-2 infection and contribute to more severe disease. The WHO’s decision followed the publication of a meta-analysis on IL-6 blockers by its Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. The meta-analysis included review of 27 randomized clinical trials using IL-6 receptor antagonists in 10,930 patients. Overall, the REACT study found that 28-day all-cause mortality was lower in patients who received IL-6 receptor antagonists than in those who did not. It is important to note, however, that the improvement in all-cause mortality was only seen when co-administered with corticosteroids. Thus, the updated WHO recommendation specifies that patients meeting criteria for severe and critical COVID-19 disease should be treated with both IL-6 receptor antagonists and corticosteroids.
BIOMARKERS Throughout the pandemic, scientists have been studying why some people are more susceptible than others to severe COVID-19 disease and what genetic factors might play into this heightened susceptibility. This week, a group of researchers with the COVID-19 Host Genetics Initiative published a study in Nature that identifies 13 genome-wide significant loci that are associated with increased risk of SARS-CoV-2 infection and with severe COVID-19 disease outcomes. The identified loci (locations of genes along chromosomes) previously have been correlated with lung function and inflammatory disorders. Understanding genetic predisposition to poor outcomes from SARS-CoV-2 infection is especially important for the development of medical countermeasures. Other studies have identified human biomarkers associated with severe COVID-19 disease whose genetic expression can be modified using existing drugs in a hospital setting. The ACE-2 receptor and associated ACE2 gene were identified early on as one such marker.
Beyond treatment of COVID-19 patients, scientists also are investigating biomarkers of successful responses to SARS-CoV-2 vaccines. Researchers at the University of Oxford who developed the AstraZeneca-Oxford vaccine are investigating the ability of their vaccine to induce high levels of neutralizing antibodies in recipients. When researchers compared vaccinated individuals who were fully protected to cases of “breakthrough infections” among other vaccinated individuals, high levels of neutralizing antibodies were correlated with better protection. Although neutralizing antibodies may not be an appropriate marker of vaccine success in other platforms, future vaccines with similar profiles to the AstraZeneca-Oxford vaccine may be able to accelerate their development if they can demonstrate high levels of this biomarker.
UK SUMMER COVID-19 PLAN On July 5, the UK announced its “Summer 2021” COVID-19 response plan, which will move the country to Step 4 of its recovery and eliminate many existing restrictions later this month. The changes are scheduled to take effect July 19, and the final decision will be made on July 12, based on updated epidemiological and other data. The decision will eliminate “all remaining limits on social contact,” including on public and private gatherings at businesses, restaurants, pubs, and other venues. Additionally, all mandates regarding mask use and physical distancing will be removed, although local health authorities can implement targeted measures in response to COVID-19 outbreaks. Beyond the social distancing-related protections, the UK also will eliminate requirements to self-quarantine after known exposure to a COVID-19 case for fully vaccinated individuals and those under the age of 18. Schools will no longer keep students in “bubbles,” and they will no longer be required to conduct contact tracing for identified cases, “which will help to minimise the number of children isolating.” The existing national testing and contact tracing program will remain in effect through the winter.
The UK plan notes that there is “a sufficiently high proportion of the population vaccinated” and that “the country can learn to live with COVID-19” without the existing restrictions. The UK reports national vaccination coverage among adults as 87% for at least 1 dose and 65% for full vaccination. Notably, UK Secretary of State for Health Sajid Javid reportedly acknowledged that removing the restrictions could result in the daily incidence exceeding 100,000 new cases per day, nearly 4 times the current average and more than 50% higher than the UK’s current record (59,829 new cases per day on January 9, 2021). The UK is currently facing its second-largest surge, which has been widely attributed to a rapid increase in the prevalence of the Delta variant (B.1.617.2). In the current surge, the UK’s daily incidence increased by a factor of 12 since mid-May, even with the existing restrictions in place.
As countries like the UK ease COVID-19 restrictions, the WHO continues to emphasize that the pandemic is far from over and urge governments to maintain effective protections. In response to the UK’s plan, more than 4,000 clinicians and other experts signed an open letter published in The Lancet, referring to the plan as “mass infection” and a “dangerous and unethical experiment” and highlighting the increased risk to children, most of whom are still not eligible for vaccination.
FIJI Fiji reported a record daily high in new COVID-19 cases on July 7, with 636 cases in 24 hours. Government officials attributed the recent outbreak to a case of the Delta variant that escaped the country’s isolation facility. Of the 39 deaths that have been reported throughout the pandemic, 37 deaths have occurred since the latest outbreak began. This newest surge is straining Fiji’s health system, where its largest hospital is now exclusively treating COVID-19 patients and its mortuary is at full capacity. Over 1,000 patients have been sent home to quarantine and recover, as medical facilities have no space. A makeshift clinic is reportedly being established, utilizing a sports arena outside the capital of Suva. The Ministry of Health has suspended all pregnancy services in and around Suva until July 26, and the ministry no longer will test residents in their homes. While no nationwide lockdown is in place, police have arrested 48 people for failure to follow local mask ordinances or limits on social gatherings. About 36% of Fiji’s population has been partially vaccinated, and just over 6% have been fully vaccinated.
OLYMPICS Two weeks from today, Tokyo will kick off its scaled-back 2020 Summer Olympic Games amid another state of emergency. The Japanese government imposed a fourth state of emergency in the Tokyo metropolitan area that will begin on July 12 and extend until August 22, through the entire Olympic Games. Olympic organizers also decided against allowing any spectators into the games, with some exceptions for events taking place in areas outside of Tokyo that are not under a state of emergency. Further changes to the Olympics programming include cancelling the Olympic torch relay through Tokyo. Athletes and other team members also must abide by strict quarantine and testing measures in order to participate. These heightened measures follow weeks of concern over rising numbers of COVID-19 cases, public opposition to the games, and consultation with experts. However, with the number of new COVID-19 cases on the upswing and vaccination rates unable to keep pace, many public health experts fear these efforts may not be enough to prevent another pandemic wave in Japan.
COMMUNIVAX The Johns Hopkins Center for Health Security is hosting the next in its series of CommuniVax webinars on July 15 at noon EDT. The webinar follows the publication of CommuniVax’s second report—The Public’s Role in COVID-19 Vaccination—and it will focus on “a new strategy for the COVID-19 vaccination campaign,” informed by input from racial and ethnic minority communities. The CommuniVax project aims to address racial and ethnic disparities in vaccination, particularly in the context of the COVID-19 pandemic. The webinar will feature presentations by and discussions with speakers representing a broad spectrum of US academic institutions and non-governmental organizations, moderated by Dr. Emily Brunson (Texas State University) and Dr. Monica Schoch-Spana (Johns Hopkins Center for Health Security). Additional information and registration is available here.
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