EPI UPDATE The WHO COVID-19 Dashboard reports 192.3 million cumulative cases and 4.14 million deaths worldwide as of 11:11am EDT on July 23.
Countries around the world are combating new COVID-19 surges, generally believed to be driven, in part, by increasing prevalence of the Delta variant (B.1.617.2). Unlike in previous surges, there do not appear to be strong regional trends, with the countries facing the largest surges distributed around the world. In fact, looking at the biweekly trends, there are approximately 50 countries where daily incidence has more than doubled, and they are spread across nearly every continent and region, with the notable exceptions of Central and South America.
In terms of total daily incidence, there are 15 countries reporting more than 10,000 new cases per day, including 6 reporting more than 25,000. Among these countries, 5 are in Asia (including Iran in the Eastern Mediterranean region), 4 are in Europe, 3 are in South America, and 2 are in North America. South Africa is the only African country, and none are in Oceania. Ten (10) of these countries are reporting increasing daily incidence over the past 2 weeks, including the US (+142%), Spain (+146%), and France (+287%), which more than doubled over that period. India and Argentina have exhibited decreasing trends since at least mid-June, and Brazil, Colombia, and South Africa passed their respective peaks since the beginning of July. These 16 countries account for nearly 75% of the global daily incidence. Among the countries with available data on the Delta variant, all* are exhibiting sharp increases in Delta prevalence over the past several months. India, where the variant was first reported, was first in March, and Delta prevalence began increasing in most of the other countries by late May/early June. Of the 10 countries with data available for July 12 or later, 8 are reporting higher than 70%, including 6 higher than 90%.
*Argentina does not have data available after May 17.
Similarly, the top countries in terms of per capita daily incidence represent most regions around the world. Among the top 20 countries, nearly half (9) are in Europe, 4 are in Africa, 3 are in Latin America and the Caribbean, and 3 are in Asia. Fiji is the only country in Oceania, and none are in North America. Argentina, Colombia, Malaysia, Spain, and the UK are on both lists, and considering their large populations compared to the other top per capita countries, this further illustrates the severity of their respective epidemics. All but 5 countries—Argentina, Colombia, Mongolia, Namibia, and Seychelles—are reporting increasing daily incidence over the past 2 weeks, including 9 that more than doubled over that period. Notably, Malta’s daily incidence increased nearly 1,500% over the past 2 weeks (peaking at more than 3,000% on July 16), bringing its daily average to approximately 200 new cases per day—up from 1 in mid-June. Only a small handful of these countries have data available regarding the prevalence of the Delta variant, and 4 of the 8 countries were also among the highest total daily incidence. All of these countries** reported major increases in Delta prevalence starting in May, and 5 of the 6 countries with data available for July 12 or later are reporting 80% or higher.
**With the exception of Argentina, which has no data available after May 17.
Global Vaccination
UNITED STATES
The US CDC reported 34.2 million cumulative COVID-19 cases and 607,684 deaths. With more than 40,000 new cases per day, the US surpassed both the peak of the initial surge—31,327 on April 12, 2020—and the low reported following the summer 2020 surge—35,082 on September 13, 2020. The current average is more than 3.5 times the most recent low on June 19 (11,467) and is still increasing steadily. Daily mortality also continues to increase, up to 223 deaths per day, which is more than 40% higher than the most recent low on July 11 (159). Notably, the proportion of emergency department patients diagnosed with COVID-19 has tripled since June 21, up from 0.6% to 1.8%, which is an indication of increasing burden on health systems*.
*In an effort to provide a more accurate analysis of the current epidemiology, we are largely focusing on longer-term trends, as the most recent data are more likely to be affected by changes in the frequency of state-level reporting, particularly over the weekend.
The US CDC added a new feature to its COVID-19 Data Tracker, which displays a combination of vaccination coverage and per capita weekly incidence at the county level. The 2-dimensional coloring scheme will take some time to interpret, but it is fairly clear that the major US COVID-19 hotspots are Missouri, Arkansas, and Louisiana, where counties are reporting lower vaccination coverage and higher weekly incidence. Alabama and Mississippi are exhibiting similar trends, but to a lesser degree. Many counties in Florida are reporting elevated weekly incidence, even with higher vaccination coverage than in neighboring states. No data are available for Texas.
US Vaccination
The US has administered 340 million cumulative doses of SARS-CoV-2 vaccines. Daily vaccinations are increasing slowly, now up to 446,613 doses per day*. A total of 187 million individuals in the US have received at least 1 dose, equivalent to 56.4% of the entire US population. Among adults, 68.6% have received at least 1 dose as well as 10.2 million adolescents aged 12-17 years. A total of 162 million individuals are fully vaccinated, which corresponds to 48.8% of the total population. Approximately 59.7% of adults are fully vaccinated, as well as 7.9 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 value provided here corresponds to 5 days ago.
DELTA VARIANT The US CDC continues to sound the alarm about the rapid spread of the SARS-CoV-2 Delta variant within the United States. Earlier this week, CDC Director Dr. Rochelle Walensky shared that the Delta variant now makes up 83% of domestically sequenced SARS-CoV-2 cases. This is a dramatic rise from the beginning of the month, when the Delta variant made up about half of sequenced cases within the US. There has been a corresponding rise in the number of new COVID-19 cases and related deaths throughout the month, especially impacting unvaccinated parts of the population. In a press conference earlier this week, Dr. Walensky warned that the Delta variant is one of the “most infectious respiratory viruses we know of,” urging individuals to get vaccinated. The CDC has made it clear that this will be another pivotal moment in the United States’ COVID-19 response, cautioning that many communities with low vaccination rates may face challenges of overwhelmed health care systems if preventative actions are not taken.
US CDC ACIP MEETING The US CDC’s Advisory Committee on Immunization Practices (ACIP) on July 22 concluded the benefits of the J&J-Janssen SARS-CoV-2 viral vector vaccine outweigh the risks of some people developing the rare neurological disorder Guillain-Barré syndrome (GBS) after receiving the shot. Earlier this month, the US FDA updated the J&J-Janssen vaccine’s label to warn of a possible increased risk of GBS. According to data presented at the meeting, the FDA’s Vaccine Adverse Event Reporting System (VAERS) recorded 100 preliminary reports of GBS after J&J-Janssen vaccination as of June 30, out of 12.6 million doses administered at that time. Of those cases, 95 required hospitalization, 1 person died, and 5 cases were non-serious. Dr. Hannah Rosenblum, a researcher with the CDC National Center for Immunization and Respiratory Diseases’ Division of Viral Diseases, presented data showing the risk of vaccine recipients developing GBS remained low when compared to the number of COVID-19 cases and deaths prevented by vaccination. The CDC plans to update its guidance for the J&J-Janssen vaccine to recommend that patients with a history of GBS first consider the 2-dose mRNA vaccines from Pfizer-BioNTech and Moderna, if possible. However, some panel members pointed out there are risks associated with those vaccines as well, including myocarditis and pericarditis, and that information on all of the risks associated with SARS-CoV-2 vaccines should be made available so people can make the best choice for themselves.
The ACIP also considered whether to recommend additional, or “booster,” doses of SARS-CoV-2 vaccines for people who are immunocompromised, who represent about 2.7% of the US population. Dr. Sara Oliver with the CDC National Center for Immunization and Respiratory Diseases presented data based on several small studies looking at vaccine response among immunocompromised people and additional doses in this population. Although emerging data suggest an additional SARS-CoV-2 vaccine dose in immunocompromised people enhances antibody response and increases the proportion who respond, the panel did not make an official recommendation on additional shots and will continue to review available data. Dr. Oliver also noted that serologic or cellular immune testing outside of research studies is not recommended in the US at this time. Some panel members expressed concern over immunocompromised patients getting additional vaccine doses without an official recommendation to do so, saying “the issue is almost running away from us.” Although another ACIP meeting is not yet scheduled, the panel is expected to meet again in August.
GAO PREPAREDNESS & RESPONSE REPORT The US is concurrently responding to and recovering from the COVID-19 pandemic, with an ongoing national vaccination campaign and widespread loosening of public health measures amid a recent increase in cases. Recognizing this balance as “fragile,” the US Government Accountability Office (GAO) on July 19 released its 7th comprehensive report on the COVID-19 pandemic, providing an additional 15 recommendations to various US government agencies. Previous reports included a total of 72 recommendations on COVID-19, with agencies agreeing to implement 57 of them and having fully implemented 16 to date. The most recent report makes several recommendations related to national pandemic preparedness, including advice to the CDC to develop a plan to enhance surge capacity for laboratory testing and establish contracts for the manufacturing and deployment of diagnostic test kits prior to public health emergencies. The GAO also made suggestions to the US Department of Health and Human Services’ (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR) regarding the organization and oversight of the country’s Strategic National Stockpile (SNS), which provides medical supplies and other materials to respond to a broad range of emergencies. Several other recommendations relate to the oversight, timely use, and integrity of COVID-19 relief funds allocated to HHS, the US Department of Education, US Department of the Treasury, US Office of Management and Budget (OMB), and Internal Revenue Service (IRS). According to GAO, if effectively implemented, the recommendations “can help improve the government’s ongoing response and recovery efforts as well as help it to prepare for future public health emergencies.”
EXPIRING VACCINES With demand for SARS-CoV-2 vaccination largely leveling off in the US over the past 3 weeks, millions of SARS-CoV-2 vaccine doses are set to expire in the next few months. Several states and some global health experts are calling for the excess doses to be redistributed to other countries, but so far the US government has rejected those requests, citing legal and logistical challenges. However, states are now able to request a specific number of vaccine doses instead of having doses distributed to them based on their population. Delayed reporting, everyday wastage, and waning demand, including those who did not go back for second doses, are among the sources for a pile up of inventory. The FDA previously extended the shelf-life of the Pfizer-BioNTech and J&J-Janssen vaccines, and some hope an additional extension for the Pfizer-BioNTech vaccine will be approved. Meanwhile, the federal stockpile of vaccine doses continues to grow, with approximately 390 million of the 1.41 billion doses purchased by the US having been delivered, and another 562 million doses from Moderna, Pfizer-BioNTech, and J&J-Janssen expected to be delivered by the end of 2021. The White House has pledged to donate 80 million doses of its vaccine supply, and will purchase an additional 500 million doses for low- and lower-middle-income countries. But some experts note the doses currently sitting in states are ready to be administered, not waiting to be manufactured, and those doses could have a positive impact in other countries if states were permitted to redistribute them.
On July 22, the American Hospital Association, the country’s largest association of hospitals and health systems, issued a statement in support of mandatory SARS-CoV-2 vaccination for healthcare workers. The statement argues that the vaccines have been demonstrated to be both safe and effective, and they play a critical role in protecting the health of both healthcare workers and their patients, many of whom are at elevated risk of severe COVID-19 disease. There have been several notable examples of hospitals firing employees who refused the vaccine, and the issue will certainly receive ongoing attention, especially until the vaccines receive full FDA approval.
VACCINE EFFICACY AGAINST VOCs A recent bioRxiv preprint study compared neutralizing antibody titers elicited by the 3 SARS-CoV-2 vaccines authorized for emergency use by the US FDA against pseudotyped variants of concern (VOCs) and variants of interest (VOIs). The small study compared blood samples from 17 people who had the 2-dose mRNA vaccines from Pfizer-BioNTech and Moderna and 10 people who received the single-dose viral vector vaccine from J&J-Janssen. Overall, the study showed a high level of antibody cross-neutralization elicited by the Pfizer-BioNTech and Moderna vaccines against VOCs but significantly decreased neutralization by antibodies generated by the J&J-Janssen vaccine. Because the study was conducted using blood samples, it might not reflect real-world performance, but the results counter previous reports of the J&J-Janssen vaccine’s efficacy against the Delta variant. The authors of the bioRxiv study, which is not yet peer-reviewed, said they hoped the findings did not discourage people from getting the J&J-Janssen vaccine but that future recommendations included advice for an additional second dose of that vaccine or an mRNA vaccine. The authors also called for continued surveillance of breakthrough infections to help determine the real-world effectiveness of the vaccines.
Another study evaluating vaccine effectiveness against the Delta variant was published July 21 in the New England Journal of Medicine. This study compared the effectiveness of the Pfizer-BioNTech mRNA vaccine and AstraZeneca-Oxford viral vector vaccine against the Alpha and Delta variants. Following 1 dose of the 2-dose vaccines, effectiveness was notably lower among persons with the Delta variant (30.7%) than among those with the Alpha variant (48.7%), with the results similar for both vaccines. Following a second dose, the Pfizer-BioNTech vaccine was 93.7% effective against Alpha and 88% effective against Delta. The AstraZeneca-Oxford vaccine after 2 doses was 74.5% effective against Alpha and 67% against Delta. The researchers note the differences in effectiveness between the vaccines are considered modest and support public health efforts to maximize uptake of the full 2-dose regimen to protect against VOCs.
REAL-WORLD VACCINE EFFECTIVENESS A study published July 20 in the Annals of Internal Medicine details a test-negative case-control study examining the short-term effectiveness of authorized SARS-CoV-2 mRNA vaccines in preventing infections. The research team used data collected through the US Department of Veteran Affairs’ (VA) COVID-19 Shared Data Resource, a national database containing extensive demographic, clinical, pharmacologic, laboratory, vital sign, and clinical outcome information derived from multiple validated sources. The researchers identified all individuals who tested positive for SARS-CoV-2 infection between December 15, 2020 and March 4, 2021, and matched them with control participants who had similar factors such as sex, age, race, BMI, and geographic location, but who had tested negative for SARS-CoV-2. The main measure of interest was vaccine effectiveness 7+ days after the second vaccine dose, but the researchers also examined vaccine effectiveness among those who received only 1 dose of either the Pfizer-BioNTech or Moderna vaccines.
The team identified 54,360 matched pairs of veterans. Among those who tested positive, 18% had been vaccinated, compared with 32.8% of those who tested negative. Overall, the vaccines showed 97.1% effectiveness among those who received the second dose at least 7 days prior. Among those who received only 1 dose, effectiveness was 85% overall. The research team concluded the SARS-CoV-2 vaccines being employed by the VA provided a high level of protection against infection. However, they noted several limitations of the study, including a predominantly male study population, a lack of data for currently circulating SARS-CoV-2 variants of concern, and a short follow-up period.
HEALTH EFFECTS OF LOCKDOWNS Researchers continue to explore the potential unintentional health impacts of COVID-19-related lockdowns. A commentary published in BMJ Global Health explores this question, comparing the costs of such lockdowns to their effectiveness in preventing COVID-19. The research team examined the issue through 4 main lenses: short-term mortality, disruption of health services, impacts on mental health, and the effect that lockdowns had on global health programs.
When examining a global dataset containing information on short-term mortality, the research team suggested that lockdowns were not associated with an increase in short-term mortality. The team specifically used Australia and New Zealand as examples, as both countries imposed strict COVID-19 lockdowns, maintained low numbers of COVID-19 cases, and had no excess mortality in 2020. When looking at disruption of health services, a topic that has garnered much attention throughout the pandemic, the authors noted that while there were notable disruptions, it was difficult to disentangle whether the lockdowns or the COVID-19 pandemic itself was the driving factor. The research team posited similar points around mental health, including suicide, stating that it was difficult to disentangle the mental health impacts of dealing with the COVID-19 pandemic with the mental health impacts of lockdowns, both of which increased increased isolation, anxiety, and stress. Lastly, the research team acknowledged that lockdowns did disrupt ongoing global health programs but, again, it was difficult to ascertain if the damage done by these disruptions outweighed the benefits associated with the COVID-19 lockdown interventions. Overall, the authors acknowledged that public health lockdowns have a real cost, but suggested they do not impart excess harm to populations facing a public health threat like COVID-19.
INDIA MORTALITY Researchers at the Center for Global Development published findings from an analysis that aimed to estimate the true COVID-19 mortality in India. India surpassed 400,000 cumulative reported deaths on July 1, but some experts are concerned that this total may be a substantial underestimate of the true COVID-19 burden, due to deficiencies in how the Indian government records mortality data—for COVID-19 and otherwise. The researchers took several approaches to estimating India’s COVID-19 mortality, including estimating excess mortality based on official death data, utilizing age-adjusted case fatality ratios and seroprevalence data, and a household-level longitudinal survey.
The mortality estimates they obtained based on these 3 methodologies ranged from 3.4 million to 4.9 million deaths, and while there are major differences between each estimate, all 3 are at least 8.5 times higher than the official data. Notably, the 3 methodologies yielded much different results for the first and second waves in India. While the second wave is generally believed to be more severe, 2 of the 3 methodologies estimate more deaths for the first wave than the second, perhaps a function of its longer duration. While these findings do not provide a definitive estimate of India’s COVID-19 mortality, this study and similar efforts continue to highlight the undercounting of COVID-19 deaths in countries around the world, and it could be years after the pandemic ends before we have a clear understanding of the global burden.
AFRICA The pace of new COVID-19 cases in Africa has slowed following an 8-week surge driven by the Delta variant, but the reprieve could be short-lived, according to the WHO Regional Office for Africa. The continent-wide decline of 1.7% this week was driven by a steep drop in the number of new cases reported in South Africa, where nationwide violence interrupted testing and, likely, reporting. The WHO warned that removing the country’s data would show an overall 18% increase in cases on the continent, creating an unbroken 9-week wave. Hospitals are overwhelmed, with few if any available intensive care unit beds, oxygen supplies are rapidly dwindling, and healthcare workers are stretched thin. South Africa stands as an example of how the long-term impacts of pandemic lockdowns on personal income, food security, and supply chains can exacerbate political instability, with the eruption of violent riots and looting in the wake of former President Jacob Zuma’s arrest earlier this month. The violence taxed an already overburdened healthcare system and disrupted COVID-19 testing and vaccination sites that were finally gaining momentum. Government officials and scientists warn the mass protests and disruptions to healthcare access could lead to another rise in COVID-19 cases, hospitalizations, and deaths.
Only about 1.5% of Africa’s population is fully vaccinated, and the continent has received less than 2% of the world’s SARS-CoV-2 vaccine doses. Data from the new Global Dashboard for Vaccine Equity estimate that African nations could add $38 billion to their gross domestic product (GDP) forecast for 2021 if they had vaccination rates similar to those in high-income countries. The inequity is creating a “two-track” pandemic and recovery, as high-income nations with higher vaccination rates are projected to recover more quickly while low- and middle-income countries (LMICs) that have not been able to access vaccines might not witness pre-pandemic growth levels until 2024, according to the UN Development Programme (UNDP), one of the dashboard’s sponsors, along with WHO and the University of Oxford. Global vaccine inequity will continue to grow under the status quo, a new analysis from the Kaiser Family Foundation shows. According to the analysis, low-income countries would need to increase their daily vaccination rate by nearly 19 times to reach 40% coverage with at least one dose by the end of the year. Ultimately, ensuring widespread vaccination will improve immunity among the global population and help bring the pandemic under control, but exactly how higher-income nations plan to increase vaccine supplies to LMICs remains an unresolved question.
VACCINE MANUFACTURING IN AFRICA Pharmaceutical company partners Pfizer and BioNTech on July 21 announced they signed a letter of intent with the Biovac Institute (Biovac)—a Cape Town, South Africa-based biopharmaceutical company—to help manufacture the Pfizer-BioNTech SARS-CoV-2 vaccine exclusively for the 55 nations of the African Union (AU). Under the plan, Biovac will “finish and fill” vaccine doses, obtaining large batch ingredients from Europe, blending the product, and filling and packaging vials for distribution, with the goal of producing more than 100 million doses annually. Pfizer-BioNTech will immediately begin to provide technology transfers, including on-site development and equipment installation, with the expectation that Biovac will be incorporated into the supply chain by the end of 2021 and begin producing finished doses in 2022. The agreement represents the first time an mRNA vaccine will be produced in Africa. Another South African firm, Aspen Pharmacare, already is producing the J&J-Janssen viral vector SARS-CoV-2 vaccine in the country, providing the same “fill and finish” services with the capacity to make more than 200 million doses each year.
The announcement received positive responses from some experts, while others called for more to be done to kickstart vaccine manufacturing in Africa. Africa CDC Director John Nkengasong said the move should be celebrated as another step in “the collective action to address technology transfer and intellectual property.” But Strive Masiyiwa, AU Special Envoy and Coordinator of the Africa Vaccine Acquisition Task Team (AVATT) initiative, called on large pharmaceutical firms to license production of SARS-CoV-2 vaccines on the continent rather than create piecemeal deals. WHO Regional Director for Africa Dr. Matshidiso Moeti also called for more local production of vaccines in Africa in order to prepare for future disease outbreaks.
Late last month, the WHO, along with Biovac, Afrigen Biologics and Vaccines, a network of universities, and the Africa CDC, established an mRNA vaccine technology transfer hub in South Africa to act as a training facility for the production of mRNA vaccine raw materials in Africa. However, neither Pfizer, BioNTech, nor Moderna, which makes another mRNA SARS-CoV-2 vaccine, has voiced support for the hub. Additionally, Pfizer reiterated the current deal with Biovac is only among the 3 companies and does not represent a government-supported technology transfer or compulsory licensing agreement. Pfizer CEO Albert Bourla on July 21 again stated the company’s opposition to a proposal at the World Trade Organization that would allow for patent waivers on SARS-CoV-2 vaccines, saying it would discourage innovation and collaboration. But BioNTech CEO Uğur Şahin indicated his company continues to evaluate sustainable approaches to supporting the African development and production of mRNA vaccines, which could be used to develop vaccines for other diseases in the future.
SARS-COV-2 ORIGINS Earlier this month, the WHO outlined a proposal for a follow-up investigation in China to identify the origins of the SARS-CoV-2 virus. On July 22, Chinese officials rejected the proposal. The WHO plan would have included additional investigations of laboratory facilities and markets in Wuhan, among other activities. Numerous governments—including the US—and experts have called for additional investigations into the origin of the pandemic, including access to additional data and specimens, arguing that limited access to the necessary data hindered the initial investigation. Following China’s rejection of the WHO proposal, the WHO called for international cooperation regarding investigations into the virus’s origins and emphasized that associated investigations are not intended to assign blame but rather to provide further understanding of how the virus emerged. As we covered previously, the WHO does not have the authority to initiate such an investigation without support from the host country.
OLYMPICS Tokyo reported its highest daily incidence since January, just as the 2020 Summer Olympics Games commence. The Tokyo Metropolitan Government reported 1,832 cases on July 21, only two days before the Olympics opening ceremony. The spike represents over 600 more cases than last Wednesday’s count. Several athletes already have tested positive for SARS-CoV-2 and will miss the Games, including a US beach volleyball player, an alternate for the US gymnastics team, and a Czech beach volleyball player. Vaccination is not required for Olympic athletes, but the Olympic playbook requires anyone going to the Games to submit two negative tests taken on separate days within 96 hours of leaving for Japan regardless of vaccination status. They are tested again upon arrival. Athletes, coaches, and officials are required to take daily antigen tests, followed by a PCR test if the antigen test returns a positive result. The Tokyo public database reports 79 people with Olympic credentials have tested positive. Close contacts of those who test positive will be allowed to train and compete as long as they receive two negative tests within 6 hours of competition.
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