COVID-19 Situation Report
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EPI UPDATE The WHO COVID-19 Dashboard reports 178 million cumulative cases and 3.9 million deaths worldwide as of 7:00am EDT on June 22. Global weekly incidence and mortality decreased for the seventh consecutive week. Global incidence fell by 5.5% compared to the previous week, and mortality decreased by 11.75%.

On June 19, Brazil surpassed 500,000 cumulative COVID-19 deaths, the second country to do so after the US. If it continues on this trajectory, Brazil could surpass the US as #1 globally in terms of cumulative mortality, but it is still approximately 100,000 deaths behind. Brazil remains #3 globally in terms of cumulative incidence; however, the US and India are both reporting declining daily incidence, whereas Brazil’s epidemic continues to accelerate. Over the past several days, Brazil surpassed India as #1 globally in terms of both daily incidence (June 17) and daily mortality (June 20). 

Global Vaccination
The WHO reported 2.4 billion doses of SARS-CoV-2 vaccines administered globally as of June 21, and 983 million individuals have received at least 1 dose. Our World in Data is reporting 2.66 billion cumulative doses administered globally, an increase of 11% compared to this time last week. The global daily doses administered is once again increasing, largely driven by trends in Asia, up to a new record high of 39.8 million doses per day. Our World in Data estimates there are 782 million people worldwide who are fully vaccinated, slightly more than 10% of the global population, although reporting is less complete than for other data.

The US CDC reported 33.4 million cumulative COVID-19 cases and 599,354 deaths. We expect the US to officially surpass 600,000 cumulative deaths in this afternoon’s or tomorrow’s update. 

The rate of decline in the United States’ COVID-19 incidence is beginning to taper off. This was inevitable as the US appears to be entering the “long tail” of its COVID-19 epidemic, but there is some concern that the slowing progress could be a function of increasing prevalence of the Delta variant of concern (B.1.617.2; VOC). The US CDC publishes genomic sequencing data, both at the national and regional levels, and this week, we will analyze trends in VOCs, including Delta, that could potentially impact COVID-19 incidence. Official data are available through May 22 and are updated every 2 weeks; however, the CDC also displays its “Nowcast” projections for the next 2-week period, through June 5. The CDC’s SARS-CoV-2 genomic surveillance represents a relatively small fraction of reported cases, so the prevalence values are weighted estimates that account for “non-random sampling of sequencing data over time and across states.”

From February 28 through May 22, the proportion of sequences corresponding to the Alpha variant (B.1.1.7) increased significantly, from 26.6% to 69.5%, becoming the dominant variant over that period. The prevalence of the Gamma variant (P.1) also increased, from 0.5% to 8.4%, the #2 variant in the US as of May 22. The proportion of sequences corresponding to the Delta variant (B.1.617.2) increased slowly from February 27 through May 22 (0.0% to 2.7%); however, it jumps to 9.9% in the CDC’s Nowcast projection for May 23-June 5, which would make it the #3 variant nationwide. If this jump is indicative of a longer-term increasing trend, the Delta variant could quickly become the dominant variant in the US. The Nowcast projection also shows another, smaller jump for the Gamma variant, from 8.4% up to 11.6%. The projected prevalence of the Alpha variant fell slightly to 65.5%, and all other variants are projected to represent fewer than 5% of new cases nationwide.

At the regional level, the Alpha variant remains the dominant strain in all 10 HHS regions as of May 22, but the Nowcast projection potentially signals major changes in the coming weeks. For the period ending May 22, the Alpha variant prevalence ranges from 51.7% in Region 1 (New England) to 76.6% in Region 7 (Central), and it is more than 70% in most regions. Interestingly, Region 7 also represents the highest Delta variant prevalence, with 7.3%. Region 3 (Mid-Atlantic) has the lowest Delta variant prevalence, with only 1.4%. In the Nowcast projection for May 23-June 5, the Alpha variant still represents more than 50% sequences in all but 1 region, with only Region 2 (New Jersey/New York) projected to be 49.7%. The projected prevalence is 50.4% in Region 1 (New England), which could indicate that the Alpha variant prevalence could soon drop below 50% in a second region. The Gamma variant is #2 in Region 1 (17.5%), and the Delta variant is #2 in Region 2 (17.7%). The Gamma variant is also currently #2 in several other regions: 6 (South Central), 7 (Central), 8 (Mountain), and 9 (West Coast). The largest increases in the projected Delta variant prevalence are in Regions 7 (Central) and 8 (Mountain), with increases of 16.2 percentage points (pp) and 19.4pp, respectively. The Gamma variant is also projected to make substantial jumps in several regions, including Region 9 (+7.2pp), Region 1 (+6.3pp), and Region 10 (Pacific Northwest; +5.3pp).

In light of inconsistencies in reporting due to the Memorial Day holiday weekend (May 29-31), it is difficult to get a clear understanding of the current trends in daily incidence. The United States’ daily incidence is at its lowest point since early in the initial surge in March 2020, and while it has exhibited a relatively consistent overall decline since mid-April, it appears that the decline could be leveling off to some degree. Prior to the Memorial Day holiday weekend, the relative biweekly change was -35%, indicating a substantial decline. Reporting delays over the holiday contributed to further declines over the next 1.5-2 weeks, which brought the relative change down to a low of -44% on June 10. Since then, it increased to -24%, still indicating a decline, but to a lesser degree than before Memorial Day.

Notably, the new federal Juneteenth holiday weekend (June 18-20) could result in further disruptions to reporting, as will the upcoming Independence Day holiday weekend (July 3-5). Juneteenth (June 19) was only officially designated as a federal holiday last week, and with little advance notice, it is unclear to what extent state and local health departments across the country were closed on Friday, June 18, in observance of the holiday. With these 3 holidays in rapid succession, it could be difficult to identify longer-term trends in SARS-CoV-2 transmission, which could potentially mask impacts from VOCs, including the Delta variant, through the middle of July.

US Vaccination
The US surpassed 150 million fully vaccinated individuals on June 21. The US has distributed 379 million doses of SARS-CoV-2 vaccines and administered 319 million. The daily vaccine doses administered* continues to decline steadily, down from a high of 3.4 million doses per day on April 11 to 855,986 on June 16. The US is averaging 581,391 new fully vaccinated individuals per day.
*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 177 million individuals in the US have received at least 1 dose of SARS-CoV-2 vaccine, equivalent to 53.4% of the entire US population. Among adults, 65.4% have received at least 1 dose, and 8.4 million adolescents aged 12-17 years have received at least 1 dose. A total of 150 million individuals are fully vaccinated, which corresponds to 45.2% of the total population. Among adults, 55.9% are fully vaccinated, and 5.8 million adolescents aged 12-17 years are fully vaccinated. Progress has largely stalled among adults aged 65 years and older: 87.3% with at least 1 dose and 77.1% fully vaccinated. In terms of full vaccination, 79 million individuals have received the Pfizer-BioNTech vaccine, 59 million have received the Moderna vaccine, and 12 million have received the J&J-Janssen vaccine.

CUREVAC VACCINE CLINICAL TRIAL On June 16, CureVac announced preliminary efficacy results from a Phase 2b/3 clinical trial of its candidate SARS-CoV-2 vaccine. CureVac is based in Germany, but the studies included approximately 40,000 participants from across 10 countries in Europe and Latin America. The vaccine demonstrated an overall efficacy of 47% against any COVID-19 disease severity, falling short of the 50% threshold established early in the pandemic.

While the CureVac candidate vaccine uses an mRNA platform similar to those used in the Pfizer-BioNTech and Moderna vaccines, the estimated efficacy is much lower, approximately half of what was observed in those vaccines’ Phase 3 clinical trials. The exact cause for the lower efficacy is unclear; however, there are some potential factors that could contribute to the disparity. First, the CureVac clinical trials were conducted at a time when variants of concern (VOCs) are more prevalent around the world, and lower efficacy against these variants would impact the overall estimate. Additionally, the CureVac product uses a much smaller dose than other mRNA vaccines—12μg compared to 30μg or 100μg in the Pfizer-BioNTech and Moderna vaccines, respectively—which could potentially limit the magnitude of the immune response. One researcher who led one of the trials in Germany indicated that the lower efficacy is “very likely due to the dose.” The mRNA used in CureVac’s vaccine was slightly different from those in other vaccines, and it did not allow for higher doses due to increased risk of adverse events.
*125 of 134 total cases have genomic sequence data available for the interim analysis.

The CureVac press release indicates that final analysis is still underway, and the company will assess potential regulatory options once that is complete. While the vaccine’s performance may be viewed as disappointing compared to similar products already authorized for use, this example illustrates the extreme difficulties in developing novel vaccines, particularly on an accelerated timeline, and it should serve as a reminder of how fortunate we are that multiple of the early vaccine candidates successfully demonstrated such high efficacy.

DELTA VARIANT OF CONCERN Experts predict the highly transmissible Delta variant of concern, also known as B.1.617.2, will become the dominant strain in the US in the near future. As select states roll back pandemic guidelines and restrictions on social gatherings, the number of Delta variant cases has roughly doubled every two weeks in the US, raising concerns among experts over the potential for breakthrough infections and localized outbreaks. US CDC Director Dr. Rochelle Walensky warned that transmission of the variant coupled with stagnating vaccination rates in some states could allow the variant to mutate enough to evade protection offered by the vaccines. Dr. Walensky and other experts continue to urge the public to get fully vaccinated, while others note an alarming trend in some states: people skipping their second dose. According to one study (preprint), 2-dose effectiveness of the Pfizer-BioNTech vaccine was 87.9% with the Delta variant, but only 33.5% after 1 dose. 

According to data from the CDC and the US Department of Health and Human Services, 5 states—Alabama, Arkansas, Missouri, Oklahoma and Utah—have experienced increases of 37% or more in their 7-day daily case averages over the last two weeks. Notably, the vaccination rates in those 5 states are lower than the national average. Currently, 45.7% of the US population has been fully vaccinated. States with higher vaccination rates, including Vermont, Hawaii, and Massachusetts, have achieved levels of population immunity that could be more successful at keeping the Delta variant at bay.

Internationally, COVID-19 cases attributable to the Delta variant are rising sharply in parts of Indonesia, including the capital Jakarta, which has seen an increase in the number of severe cases among younger adults. In Europe, experts are closely watching spikes in SARS-CoV-2 cases driven by the Delta variant. Officials in the UK and Portugal have reimplemented or held off on lifting lockdown measures due to an increasing number of cases, and experts in France, Germany, and Spain are monitoring clusters of Delta cases. The greater transmissibility and disease severity of the Delta variant could cause outbreaks to grow more serious more quickly than surges caused by previous variants.

GLOBAL COLLABORATION On June 21, the WHO and its COVAX partners announced they are working with a South African consortium to establish the African continent’s first COVID-19 mRNA vaccine technology transfer hub, aimed at scaling up SARS-CoV-2 vaccine production. Over the coming weeks, the partners—including Biovac, Afrigen Biologics and Vaccines, a network of universities, and the Africa CDC—will negotiate details with the government of South Africa and other stakeholders. The hub is expected to provide training and knowledge transfers on mRNA technologies that would allow manufacturers in low- and middle-income countries to produce the vaccines locally. However, the hub still needs to secure licensing agreements with vaccine manufacturers, notably Pfizer-BioNTech and Moderna, according to WHO officials, who noted those discussions are underway. Manufacturing at the South African hub is expected to begin in 9-12 months. South Africa President Cyril Ramaphosa praised the hub’s launch, calling it a historic step in the right direction, but he urged continued discussions on an intellectual property waiver under the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights, or TRIPS.

At the conclusion of this past weekend’s Summit for Vaccine Internationalism, led by countries from the global south, national health officials committed to openly collaborate on SARS-CoV-2 vaccine technologies, pool manufacturing capacity for vaccines and other medical supplies, and provide regulatory capacity support. Cuba and Mexico pledged to offer open licenses for their domestically developed vaccines, and Venezuela proposed creating a technology transfer platform similar to the WHO’s COVID-19 Technology Access Pool. While the COVID-10 pandemic has spurred remarkable and rapid collaboration among a variety of partners, some researchers are expressing concern that the benefits of collaboration could be hindered by geopolitical tensions and are not always shared equally. Additionally, global health experts continue to call for more robust efforts to increase access to and production of vaccines in low and middle income countries, underlining the mantra that the pandemic will not end until it’s under control in every country.

SOUTH AMERICA COVID-19 is surging across South America, which accounts for only 5% of the world’s population but 25% of the pandemic's death toll. Collectively, the region’s death rate per capita is 8 times the world’s rate. Nearly 1 million people have died of COVID-19 across 12 countries in South America, and the region holds 7 of the 10 countries worldwide with the highest daily death rates per capita.

In Brazil, tens of thousands of protestors took to the streets of cities nationwide on Saturday, with demonstrators blaming Brazil President Jair Bolsonaro for dismissing the seriousness of the pandemic. The Brazilian Senate is investigating President Bolsonaro’s handling of the nation’s pandemic response, including accusations he purposefully delayed vaccination efforts. Brazil passed 500,000 COVID-19-related deaths this past weekend, second only to the US and India, where the official death toll is 389,302 but is estimated to be up to 4.2 million. Nearly 18 million people have been infected with SARS-CoV-2 in Brazil, and the country is experiencing a daily average of nearly 73,500 new cases and around 2,000 deaths. Only 11.5% of residents are fully vaccinated. Notably, Brazil’s outbreak is being fueled by the Gamma variant, also known as P.1, which was first identified in the country’s Amazon region. The Oswaldo Cruz Foundation (Fiocruz), part of the nation’s Ministry of Health, warned the situation is “critical” and the onset of winter could result in even more infections. 

PHILIPPINES VACCINATION According to multiple news media reports, Philippines President Rodrigo Duterte recently indicated that he could begin arresting individuals who refuse SARS-CoV-2 vaccination. President Duterte is known for “brash rhetoric,” but he has demonstrated the willingness to take extreme measures to combat other threats, such as his “war” on drugs. The extent to which President Duterte can or will implement efforts to mandate vaccinations remains unclear. In comments earlier this week, he indicated that he would direct local government officials to compile lists of individuals who refuse vaccination. Mandatory vaccination policies pose a number of practical and ethical challenges, and many experts argue that they may not necessarily be the best option for increasing vaccination coverage, particularly from the perspective of establishing trust in the government and response. The Philippines has administered at least 1 dose of SARS-CoV-2 vaccine to approximately 5.7% of its population, and nearly 2% are fully vaccinated

LONG COVID/PASC Studies are ongoing to improve our understanding of the longer-term physical and mental health effects of SARS-CoV-2 infection. Previous studies have documented cardiovascular, respiratory, and neurological symptoms that can persist for months after recovery from SARS-CoV-2 infection, including in individuals who experienced mild or asymptomatic COVID-19 disease. A study conducted by FAIR Health investigated private health insurance claims associated with “Long-Haul COVID.” The study included nearly 2 million COVID-19 patients and looked for the presence of COVID-19-related symptoms 30 days or longer after recovery from acute COVID-19 disease. The researchers found that 23.2% of COVID-19 patients reported at least 1 symptom 30 days or longer after recovery. The prevalence of persistent symptoms was higher among patients with severe COVID-19, but persistent symptoms also were present in patients who were asymptomatic or mildly symptomatic during the acute stage of their infection. Additionally, patients of all ages were affected by longer-term health effects, including children.

Researchers in the UK found that COVID-19 could be associated with the loss of brain tissue after recovery, even among individuals with mild COVID-19 disease. The study (preprint) utilized brain scans taken as part of an ongoing Biobank study. The researchers compared scans taken before infection and after recovery for 394 COVID-19 patients, and compared them with 388 healthy control participants. The study documented loss of grey matter brain tissue in recovered COVID-19 patients, compared to the controls. The effects were observable in multiple parts of the brain, including areas that could potentially increase the risk of Alzheimer’s disease or dementia later in life. The researchers also compared hospitalized and non-hospitalized COVID-19 patients. There was potential evidence of an association between disease severity and brain tissue loss, but it was not statistically significant. Notably, there were only 15 hospitalized patients included in the study, which limited the available data. The availability of brain imagery from before the pandemic provided the researchers with an opportunity to directly observe changes in brain tissue in individuals who were later infected with SARS-CoV-2.

MONOCLONAL ANTIBODY TREATMENT Regeneron’s monoclonal antibody (mAb) combination treatment appears to reduce deaths in COVID-19 patients who are unable to mount their own antibody response, according to RECOVERY trial preliminary results. In the clinical trial, 24% of patients given a combination of two monoclonal antibodies (casirivimab and imdevimab) died, compared with 30% of patients given standard care (rate ratio 0.80; 95% CI 0.70–0.91; p=0.001). The study also saw a reduction in the median length of hospital stays for those given the treatment compared to the control group. Patients receiving Regeneron’s treatment also were significantly less likely to require mechanical ventilation

While mAbs have been available for use during the majority of the pandemic, their relative effectiveness in decreasing deaths or improving clinical markers has been debated. Previous studies have shown that some patients greatly improve following mAb infusion while others show no improvement at all. The US government had previously purchased 1.5 million doses of the combination therapy after it received emergency use authorization from the FDA, but those doses have widely gone unused. With the availability of antibody tests, hospitals can now test COVID-19 patients for evidence of an antibody response, or lack thereof. In those patients with no discernible antibody response, the REGEN-COV could be a potentially life saving intervention. However, the therapy’s high price (around $1,400 per treatment) likely will inhibit greater uptake in high-income countries and could be cost-prohibitive in developing countries.

MODERNA VACCINE The US government recently signed an agreement to purchase 200 million more doses of the Moderna vaccine, including an option to buy experimental doses in development. The US order brings the nation's total number of Moderna doses purchased to 500 million. Moderna thus far has provided 217 million doses to the US and is expanding its manufacturing capacity to fulfill this contract and others in the future. Moderna has added two new production lines to its plant in Boston, Massachusetts. These and other additions will increase its manufacturing capacity by 50% by the end of 2022. Moderna is currently developing booster shots and other experimental vaccines aimed at targeting newer SARS-CoV-2 variants. 

US CDC CRUISE SHIP REGULATION A federal judge on June 18 ruled the US CDC cannot enforce its COVID-19 conditional sailing orders—under which cruise lines were required to implement a phased approach to testing and other safety measures before they could start sailing—that were intended to prevent the spread of SARS-CoV-2 on Florida-based cruise ships. Florida challenged the CDC rules in April, arguing they were obstructing the cruise industry’s operations and causing the state to lose hundreds of millions of dollars. In his ruling, US District Court Judge Steven D. Merryday sided with the state, issuing a preliminary injunction to begin on July 18, when the conditional sailing order will exist only as non-binding guidelines. Judge Merryday wrote in the 124-page decision, “In a word, never has CDC implemented measures as extensive, disabling, and exclusive as those under review in this action.” The ruling orders both parties to return to mediation to work out a final solution, efforts that have previously failed; however, the CDC could appeal the decision. On June 16, the CDC lowered its risk level guidance from Level 4 “Very High” to Level 3 “High” for cruise ship passengers who are not fully vaccinated.  

SUMMER OLYMPICS & WORLD CUP The 2020 Summer Olympic Games are slated to proceed in Tokyo despite rising concerns over Japanese vaccination rates and the nation’s current burden of COVID-19 cases. Olympic organizers announced some local fans will be allowed at events under strict rules, including mask wearing, no cheering, and returning directly home. Stadiums and other venues will be limited to 50% capacity or up to 10,000 domestic fans, whichever is less. Spectators will be allowed only if no state of emergency is in effect, and the rules could change as vaccinations increase or if a surge is predicted. Japan is advancing efforts to improve national vaccination rates, with 33 million inoculations to date and 7.7% of the population fully vaccinated. 

As the international community looks to future sporting events, Qatar has stated that only vaccinated fans will be allowed at the 2022 World Cup, posing a substantial barrier for players and fans from many low- and middle-income countries who have yet to be vaccinated. Qatar is in the process of securing 1 million SARS-CoV-2 vaccine doses in case global efforts lag. FIFA President Gianni Infantino said the November 2022 matches are expected to be held in full stadiums. Qatar has fully vaccinated 45% of its population to date.