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EPI UPDATE The WHO COVID-19 Dashboard reports 121.5 million cases and 2.7 million deaths as of 11am EDT on March 19.

Many countries in central and eastern Europe are exhibiting what could be the early signs of a “third wave” of COVID-19. Looking at the relative change in daily incidence, most European countries were still combating the autumn 2020 surge in November 2020 and then turned a corner in December 2020 and January 2021. By late February/early March 2021, however, incidence in many European countries began to increase again. Unlike the period between Europe’s first and second waves—during which many European countries maintained low levels of transmission over a period of months—the most recent decline barely fell below half of the autumn 2020 peak, and only briefly, before increasing again.

Not all European countries are exhibiting increasing daily incidence, but many are. A number of countries that are experiencing a surge exhibit a similar epidemic trajectory. These countries tend to peak between early November and early December, followed by a steady decline into 2021 and then a surge beginning in early-to-mid February 2021. A number of European countries exhibit this trend, including Austria, Bosnia and Herzegovina, Bulgaria, Greece, North Macedonia, Romania, Serbia, and Ukraine. In some of these instances, the current surge is quickly approaching the peak of the autumn 2020 surge, which accounted for the most severe portion of the pandemic in many European countries.

In terms of total daily incidence, a number of larger European countries stand out. France’s daily incidence has steadily increased since it came down from its autumn 2020 surge in early December 2020, while the surges in other countries started closer to mid-February 2021. In Hungary, for example, the daily incidence increased from approximately 1,500 new cases per day in mid-February to more than 7,700, an increase of more than 400%. In Poland, the daily incidence has more than tripled since mid-February, up from approximately 5,400 new cases per day on February 13 to more than 17,000 (and still increasing steadily). Italy’s daily incidence nearly doubled over the past month, although it appears to be tapering off to some degree.

Looking at the per capita daily incidence, it is evident that smaller countries are facing similar surges. Estonia never really came down from its autumn/winter 2020 surge. Rather, it plateaued in late December 2020 and then surged again starting in early February. At its low in October 2020, Estonia reported 28 new cases per day, which increased to approximately 600 in late 2020/early 2021 and then increased again to more than 1,400 new cases per day currently. Czechia is battling its third COVID-19 spike since October, the most recent of which started in early-to-mid February. Each spike peaked at approximately 12-13,000 new cases per day, and the current spike appears to be starting to decline.

At this point, the major drivers of the ongoing surge remain uncertain. It is likely a combination of a number of factors, including geographic and community spread of emerging variants that exhibit increased transmissibility, and increased social interaction due to relaxing COVID-19 restrictions that were put into place following the autumn 2020 surge. European countries continue to scale up vaccination efforts, but many experts and government officials have noted the slow distribution process across the continent, which is negatively impacting governments’ ability to increase vaccination coverage. At this point, it appears that many European countries have not yet achieved sufficient vaccination coverage to begin containing their respective epidemics, and it will be critical to both increase vaccine supply and vaccination capacity and maintain necessary protective measures over the coming months, particularly as many European countries look ahead to the summer tourist season.

Global Vaccination
The WHO reported 364.2 million vaccine doses administered globally, including 207.8 million individuals with at least 1 dose. The dashboard does not yet include daily or weekly vaccinations.

Our World in Data reports that 409.8 million vaccine doses have been administered globally, a 21% increase compared to this time last week. The daily average surpassed 10 million doses per day. The current average of 10.3 million doses per day is a 40% increase compared to a week ago. At least 143 countries and territories are reporting national vaccination data.

The US CDC reported 29.4 million cumulative cases and 535,217 deaths. Daily incidence continues to level off, although it may still be decreasing slowly. After falling from nearly 250,000 new cases per day to fewer than 64,000 between January 11 and February 22, the national average has decreased just 9,998 new cases per day since then. The current daily decline of 435 fewer new cases per day since February 22 is approximately one-tenth of what it was previously (4,420 fewer new cases per day). Daily mortality continues to decrease as well, but it may have passed an inflection point and appears to be starting to taper off slightly. On March 16, the average daily mortality fell below the peak of the summer 2020 surge.

US Vaccination
The US CDC reported 151.1 million SARS-CoV-2 vaccine doses distributed and 115.7 million doses administered. This includes 75.5 million people (22.7% of the entire US population; 29.2% of the adult population) who have received at least 1 dose of the vaccine, and 41.0 million (12.3%; 15.9%) who are fully vaccinated. Among adults aged 65 years and older, nearly two-thirds (66.3%) have received at least 1 dose and 38.6% are fully vaccinated.

The average doses administered* appears to be leveling off at approximately 2.2 million doses per day, including 902,781 individuals fully vaccinated (ie, second dose of a 2-dose vaccine or a single dose of a 1-dose vaccine). In terms of full vaccination, 20.5 million individuals have received the Pfizer-BioNTech vaccine, 19.4 million have received the Moderna vaccine, and 2.0 million have received the J&J-Janssen vaccine.
*The US CDC does not provide a 7-day average for the most recent 5 days due to anticipated reporting delays for vaccine administration. This estimate is the most current value provided.

A total of 7.6 million doses have been administered at long-term care facilities (LTCFs)**, including residents and staff. This covers 4.8 million individuals with at least 1 dose and 2.8 million with 2 doses. Vaccination progress at LTCFs has slowed considerably, as the available vaccine supply is shifting toward lower-tier priority groups and the broader public.
**The dashboard only includes data for doses administered through the Federal Pharmacy Partnership for Long-Term Care (LTC) Program. It does not report data from West Virginia, which opted out of the program.

The Johns Hopkins Coronavirus Resource Center is reporting 29.7 million cumulative cases and 539,868 deaths as of 12:30pm EDT on March 19.

ASTRAZENECA-OXFORD VACCINE IN EUROPE After a number of countries paused vaccination efforts using the AstraZeneca-Oxford SARS-CoV-2 vaccine, health experts raised concerns that these decisions were not consistent with the available scientific evidence. While countries in Europe were the first to suspend their vaccinations, some countries in Africa reportedly took similar measures. Following reports of several instances of blood clotting conditions in recently vaccinated individuals, the European Medicines Agency (EMA) initiated a study of the available evidence to assess any safety issues with the vaccine.

On March 18, the EMA issued a statement regarding its preliminary findings. The analysis found no association between the vaccine and increased risk of blood clots (thromboembolic events), and there was no evidence that the clotting events were associated with a specific batch of the vaccine. The EMA did identify a potential association between the vaccine and “very rare cases of blood clots associated with thrombocytopenia, i.e. low levels of blood platelets...including rare cases of clots in the vessels draining blood from the brain (CVST),” but further analysis is needed. The EMA reviewed data from 7 cases of individuals with multiple blood clots and 18 cases of CVST out of approximately 20 million vaccinated individuals. It emphasized that COVID-19, itself, is associated with potentially fatal blood clotting conditions and that the benefits of vaccination outweigh the risk of adverse events. 

The WHO also issued a statement on the vaccine, emphasizing that the vaccine “will not reduce illness or deaths from other causes” and that thromboembolic events “occur frequently.” Following its own analysis, Africa CDC issued a recommendation that all African Union countries continue vaccination efforts using the AstraZeneca-Oxford vaccine. At least a dozen European countries have reportedly resumed use of the vaccine this week. But even as countries resume use of the vaccine, health experts are concerned “the damage is done” and that decisions to suspend the use of the vaccine will have lasting effects on public confidence in the vaccine.

While other countries were curtailing their use of the AstraZeneca-Oxford vaccine, Canada announced it is expanding its use in older adults. Previously, Canada’s National Advisory Committee on Immunization (NACI) did not recommend the vaccine for adults over the age of 65 due to insufficient evidence, but it issued the update based on real-world data from ongoing vaccination efforts.

US LOANS ASTRAZENECA-OXFORD VACCINE The US government is finalizing plans to ship millions of doses of its available AstraZeneca-Oxford SARS-CoV-2 vaccine supply to Mexico and Canada. During a March 18 press conference, White House Press Secretary Jen Psaki said the US has 7 million available doses and plans to send 2.5 million doses to Mexico and 1.5 million doses to Canada. She noted that the shipments would amount to a loan, with the US expected to receive doses of the same or a different vaccine in the future, and that the US government’s first priority remains vaccinating the US population. The US has faced increasing pressure to share its supply of vaccines with other countries, particularly the AstraZeneca-Oxford vaccine, which is not yet authorized for use in the US. Ms. Psaki said the White House continues to engage in conversations regarding requests from other countries, but providing the vaccine to US neighbors to the north and south is in the country’s best interest. The plan could be finalized as soon as today.

GLOBAL VACCINE PRODUCTION On March 17, a group of Democratic members of the US House of Representatives urged President Joe Biden to support an emergency temporary waiver of some World Trade Organization (WTO) Trade-Related Aspects of Intellectual Property Rights (TRIPS) rules, which they argue would increase global production of vaccines, treatments, and diagnostic tests for SARS-CoV-2. At issue is a joint India-South Africa proposal to the WTO TRIPS Council that would provide a temporary intellectual property waiver for equipment, drugs, and vaccines related to the COVID-19 pandemic. While the proposal is supported by more than 50 low- and middle-income countries (LMICs), Western nations have blocked the proposal 8 times, the latest on March 10. Proposals need a consensus of at least 164 countries to pass. The TRIPS Council is scheduled to meet again June 8-9, when the proposal could be addressed again. 

Though the idea to issue intellectual property waivers seems simple and is supported by multiple international organizations—including Oxfam, Médecins Sans Frontières (MSF), and the WHO—some experts and pharmaceutical companies argue the benefits of the move are not clear-cut. The Pharmaceutical Research and Manufacturers of America (PhRMA) says there is no evidence that waivers would increase vaccine production or access. In fact, some experts believe waiving intellectual property rights could backfire and cause some companies to disengage from global access efforts. Instead, some experts suggest that voluntary licensing agreements, under which vaccine developers can enter into manufacturing contracts with generic producers, could be a solution. They emphasize that cooperation and smart incentives, and not the elimination of intellectual property rights, is the best route to increasing production and access to COVID-19 medical products.

MODERNA VACCINE CLINICAL TRIALS Moderna announced that it administered the first doses of its SARS-CoV-2 vaccine to pediatric participants in a Phase 2/3 clinical trial. The study will include 6,750 children aged 6 months to less than 12 years enrolled at sites in the US and Canada. The study will begin by evaluating multiple vaccine doses, including 3 different doses (25μg, 50μg, and 100μg) in children under 2 years old and 2 different doses (50μg or 100μg) for children 2 years and older. Interim analysis will determine which doses will be used in the larger study.

Moderna also announced it commenced a Phase 1 clinical trial for its “next generation” SARS-CoV-2 vaccine. The new vaccine candidate utilizes an mRNA platform, like Moderna’s existing vaccine, but it aims to be stable at normal refrigerator temperatures rather than freezer temperatures like the current vaccine. Moderna intends to conduct future clinical trials to evaluate the new candidate’s efficacy as both a standalone vaccine and as a booster for its existing vaccine. Moderna also started a Phase 2 clinical trial of a modified version of its existing vaccine that aims to serve as a booster dose to increase efficacy against the B.1.351 variant. The trial includes 3 arms testing multiple formulations of the new candidate, including 20 µg and 50 µg doses of the variant-specific booster candidate and a multivalent booster candidate, which contains mRNA for “ancestral strains” and the B.1.351 variant.

VACCINE EFFICACY ON EMERGING VARIANTS Researchers in South Africa—in collaboration with researchers in the UK, including from AstraZeneca and the University of Oxford—published findings from a study of the AstraZeneca-Oxford vaccine’s efficacy against the B.1.351 variant. The study, published in The New England Journal of Medicine (NEJM), was a randomized, placebo-controlled clinical trial, and it included nearly 1,500 participants aged 18-65 years who had not been previously infected in the primary analysis. The study enrolled participants from June-November 2020.

The vaccine exhibited an overall efficacy of 21.9% against any COVID-19 disease, with 19 cases among 750 vaccinees compared to 23 cases among 717 participants in the control group; however, the efficacy results did not demonstrate a statistically significant benefit. There were no cases of severe disease or death in either group. Of 41 cases with sequencing data available, 39 (95.1%) were caused by the B.1.351 variant, suggesting the vaccine efficacy against this variant to be 10.4%, but again, the results did not demonstrate a statistically significant level of protection. In contrast, the researchers also looked at data from before the B.1.351 variant was widespread in South Africa. Using cases detected on October 31, 2020 or earlier as a “proxy for non-B.1.351 variant” infection, they estimated an efficacy of 75.4%.

While further analysis is needed to more fully characterize the efficacy of all available vaccines against emerging variants, this study provides further evidence that variants of concern (VOCs), like B.1.351, could pose significant challenges in terms of containing COVID-19 through vaccination. Efforts are ongoing to update the AstraZeneca-Oxford and other vaccines to provide better protection against emerging variants. 

EMERGING VARIANTS On March 16, the US CDC updated its information on emerging SARS-CoV-2 variants. The CDC introduced classifications for emerging variants: Variants of Interest, Variants of Concern, Variants of High Consequence. Variants of Interest have “genetic markers” that could potentially affect transmissibility, disease severity, or susceptibility to vaccines or therapeutics, whereas Variants of Concern include those for which there is existing evidence of increased transmissibility, disease severity, or reduced susceptibility. Variants of High Consequence are limited to variants with clear evidence of reduced effectiveness for risk mitigation measures or medical countermeasures (MCMs). The CDC has classified 3 variants—B.1.526, B.1.525, and P.2—as Variants of Interest and 5 variants—B.1.1.7, P.1, B.1.531, B.1.427, and B.1.429—as Variants of Concern. Notably, the previous CDC guidance, prior to its tiered classification system, included only B.1.1.7, P.1, and B.1.351 as Variants of Concern, and the 2 new additions are variants that were first identified in California. There are currently no Variants of High Consequence.

Two recently published studies found evidence of increased mortality linked to the B.1.1.7 variant. The first study, published in Nature, included data from 2.2 million positive SARS-CoV-2 tests in England from November 2020 to February 2021, including nearly 17,500 deaths. The researchers estimate an increase in mortality of approximately 60% associated with the B.1.1.7 variant (adjusted hazard ratio=1.61). The second study, published in The BMJ, matched nearly 55,000 pairs of participants in the UK to compare the mortality of the B.1.1.7 variant against others. The researchers paired participants based on the ability of the TaqPath diagnostic assay to detect the spike protein gene as a proxy for B.1.1.7 infection to ensure each pair included one and only one B.1.1.7 infection. These researchers also estimated an increase in mortality of approximately 60% associated with the B.1.1.7 variant (adjusted hazard ratio=1.64). The researchers note that this change represents an increase in deaths from 2.5 to 4.1 per 1,000 detected cases. 

INTERNATIONAL TRAVEL GUIDANCE On March 18, WHO officials announced they are working on the development of a “smart vaccination certificate” for people who have received a SARS-CoV-2 vaccine. WHO Regional Director for Europe Dr. Hans Kluge emphasized that this effort is simply a method of documenting vaccination status and not a “vaccine passport.” The vaccination certificate should not be mandatory for international travel. There still remains a global shortage of vaccines, which would put travelers from some countries at a disadvantage if it were mandatory, and the duration of vaccine-induced immunity is still highly uncertain, which poses a technical barrier for a mandatory vaccine passport. In a WHO webinar on international travel during the COVID-19 pandemic, a representative of the WHO Smart Vaccination Certificate Working Group said the group intends to solicit public comment to inform its discussions starting today.

The WHO’s distinction on vaccine certificates versus passports came one day after the European Commission (EC) proposed delivering free “Digital Green Certificates” that would allow EU residents to travel freely within the bloc. The certificates would be made available to those who have been vaccinated as well as those who test negative for the virus or have recovered from natural infection. Some countries have expressed opposition to the plan, considering many individuals have not yet been able to access the vaccine, but the EC noted that vaccination would not be mandatory for EU citizens to travel between EU countries. The plan is set to be discussed next week at a summit of EU leaders. A WHO official noted the agency is looking into the details of the EC plan. 

In the US, Senior Advisor for the White House COVID Response Team, Andy Slavitt, suggested that the government should not be involved in verifying individuals’ vaccination status nor in issuing certification. Though Americans will need a way to document vaccination, Slavitt indicated that the process should be private, secure, free, available digitally and on paper, and available in multiple languages.

GLOBAL COVID-19 MORTALITY Analysis published by Think Global Health puts global COVID-19 mortality in the context of other major causes of death. To date, the WHO has reported more than 2.6 million cumulative COVID-19 deaths worldwide, including 1.8 million in 2020. Since the onset of the pandemic, COVID-19 has accounted for 4.4% of all reported deaths globally, making it the fourth leading cause of death over that period, following ischemic heart disease (15.5%), stroke (11.1%), and chronic obstructive pulmonary disease (COPD; 5.6%). Notably, COVID-19 was the leading cause of death in some parts of the world, including nationally in France, Mexico, Spain, and the UK as well as half of the countries in South America and some US states. The proportion of deaths due to COVID-19 varies widely by region. Not surprisingly, the Americas, led by the US and Brazil, has the highest proportion of deaths due to COVID-19 (13.0%), followed by Europe (9.3%). The Eastern Mediterranean region (3.0%), Southeast Asia (2.3%), Africa (0.8%), and the Western Pacific region (0.2%) are all below the global average. Notably, COVID-19 was outside of the top 50 or top 100 causes of death in most countries in Africa, south and southeast Asia, and Oceania. Overall, COVID-19 was the 24th leading cause of death in Africa.

US VACCINE ELIGIBILITY AND ACCESS Due to variability across US states in both demographics and vaccine allocation strategy, some states are beginning to move into different phases of their SARS-CoV-2 vaccine rollout. Earlier this week, Mississippi joined Alaska as the second state to open COVID-19 vaccination to all adults ages 16 and older, having reached target thresholds for higher priority groups. US President Joe Biden has called for all states to open vaccination to all adult residents by May 1, as vaccine supply and administration continue to ramp up. Some states, like Ohio, Indiana, and Wisconsin, are opening their vaccination eligibility to larger groups of adults, with specific requirements varying among states. Other states are announcing wider eligibility standards for the coming weeks or months. 

Despite these promising announcements, challenges persist around availability of appointments and equitable vaccine access. In a report published in the US CDC’s MMWR, the US CDC COVID-19 Response Team examined county-level vaccination coverage based on the CDC’s Social Vulnerability Index (SVI) score, which uses 15 socioeconomic, demographic, and other indicators “to help local officials identify communities that may need support before, during, or after disasters.” The researchers found that SARS-CoV-2 vaccination coverage was lower in high vulnerability counties than in low vulnerability counties, with an overall difference of 1.94 percentage points. The largest coverage disparities were associated with socioeconomic disparities, with vaccination coverage 2.5 percentage points higher in low vulnerability counties than high vulnerability counties. The researchers called for increased attention to achieving equity in vaccine administration.

At a more granular level, advocates continue to question why incarcerated individuals are lower on the priority list for SARS-CoV-2 vaccination. Some argue that prisons should be considered as long-term care facilities (LTCFs), just like nursing homes, due to the elevated risk of transmission and elevated rates of underlying health conditions associated with higher risk of severe disease and death. According to a report by STAT News, 19 states do not plan to administer SARS-CoV-2 vaccines to incarcerated populations until they finish with the broader public. The high COVID-19 risk for incarcerated populations and risk of community outbreaks originating in correctional facilities underlie the need for vaccination prioritization.

US CDC SCHOOL PHYSICAL DISTANCING GUIDANCE The US CDC published updated guidance for physical distancing in K-12 classrooms, which reduces the recommended physical distancing in some settings from 6 feet to 3 feet. Earlier this week, Chief Medical Advisor to the President Dr. Anthony Fauci and CDC Director Dr. Rochelle Walensky indicated that the CDC was considering the change, based on evolving evidence about transmission risk in school settings and notable challenges facing schools in terms of maintaining 6-foot separation for students and staff. The changes were based in part on the findings from several studies published in today’s MMWR, which provide further evidence regarding SARS-CoV-2 transmission dynamics in school settings. In addition to physical distancing, the new guidance includes updates regarding improved ventilation, physical barriers, and other aspects of COVID-19 mitigation in schools.

The updated guidance indicates that elementary schools can reduce physical distancing to 3 feet as long as mask use is universal, regardless of the level of community transmission. For middle and high schools, in classrooms where mask use is universal, the CDC recommends 3-foot separation in schools where community transmission is low, moderate, or substantial. For middle and high schools in areas where community transmission is high, the CDC recommends 6-foot separation if cohorting—ie, keeping the same groups of students together throughout the day to reduce mixing with other groups—is not possible. Schools in high-transmission areas that are able to implement cohorting strategies can operate using 3-foot distancing.

The CDC continues to recommend 6-foot physical distancing between adults, in common areas (eg, lobbies, auditoriums), when masks cannot be worn (eg, when eating), and during activities that involve “increased exhalation” (eg, singing, band practice/performance, sports practice/competition). Reducing the recommended physical distancing separation to 3 feet aims to make it easier for schools to resume in-person classes while continuing to mitigate transmission risk.