COVID-19 Situation Report
The Center also produces US Travel Industry and Retail Supply Chain Updates. You can access them here.
Editor’s Note: Our COVID-19 Situation Report team is taking a break next week. We will be back on Tuesday, June 8, with our curated analysis of the latest COVID-19 news and research.

Thanks to our wonderful team who pulls these together: Alyson Browett, Natasha Kaushal, Amanda Kobokovich, Margaret Miller, Christina Potter, Dr. Caitlin Rivers, Matthew Shearer, Marc Trotochaud, and Rachel Vahey.
EPI UPDATE The WHO COVID-19 Dashboard reports 167 million cumulative cases and 3.5 million deaths worldwide as of 4:45am EDT on May 25. Global weekly incidence and mortality continue to decline, both for the third consecutive week. The weekly incidence decreased 14% from the previous week, and weekly mortality decreased by 2%.

Global Vaccination
The WHO reported 1.49 billion doses of SARS-CoV-2 vaccines administered globally as of May 24, and 700 million individuals have received at least 1 dose. Our World in Data reported 1.70 billion cumulative doses administered globally. The global cumulative total continues to increase at approximately 13% per week. Daily doses administered continue to increase, up to a new record of 28.4 million doses per day on May 22 before falling slightly to 28.1 million. The global increase is largely driven by Asia, which, in turn, is largely driven by China. Our World in Data estimates there are 395 million people worldwide who are fully vaccinated, corresponding to approximately 5.1% of the global population, although reporting is less complete than for other data.

The US CDC reported 32.9 million cumulative cases and 587,342 deaths. Daily incidence continues to decline, to the lowest levels since early in the pandemic. The current average daily incidence—22,877 new cases per day—is the lowest since June 14, 2020. The lowest daily incidence between the United States’ first and second surge was 20,733 on June 1, 2020, and the US could fall below that average in the coming days, if it continues on this trajectory. After falling below 500 deaths per day on May 20, daily mortality increased slightly, up to 508 on May 22 before falling back to 500.

US Vaccination
The US has distributed 357 million doses of SARS-CoV-2 vaccines and administered 287 million. After more than a month of decline, the daily doses administered* has increased for 5 consecutive days, back up to 1.7 million doses per day. The increase over the past several days is due to an increase in the number of first doses administered—up from 554,890 individuals per day on May 12 to 882,463 on May 19, an increase of nearly 60% over that period. Approximately 953,000 people are achieving fully vaccinated status per day, down from a high of 1.8 million per day on April 12. If this level of interest is sustained from the first to the second dose, we could expect to see an increase in the number of fully vaccinated individuals each day starting in the next 2-3 weeks, once second doses are administered.

A total of 164 million individuals in the US have received at least 1 dose of SARS-CoV-2 vaccine, equivalent to 49% of the entire US population. Among adults, 62% have received at least 1 dose, and 5.2 million adolescents aged 12-17 years have received at least 1 dose. A total of 131 million people are fully vaccinated, which corresponds to 39% of the total population. Among adults, 50% are fully vaccinated, and 2.0 million adolescents aged 12-17 years are fully vaccinated. Progress has largely stalled among adults aged 65 years and older: 85% with at least 1 dose and 74% fully vaccinated. In terms of full vaccination, 67 million individuals have received the Pfizer-BioNTech vaccine, 53 million have received the Moderna vaccine, and 10.2 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.

Following updated guidance from the US CDC regarding recommendations for fully vaccinated individuals, US states are moving forward with efforts to relax or remove COVID-19 restrictions. However, US states vary widely in terms of vaccination coverage, and increased social interaction among unvaccinated individuals could increase risk of community transmission. The full vaccination coverage in states at the top of the rankings is nearly double the coverage in states at the bottom, ranging from 26.5% to 52.7%. There are 4 states currently reporting full coverage greater than 50%—Vermont (52.7%), Connecticut (51.6%), Maine (51.9%), and Massachusetts (50.5%)—and Rhode Island is nearly there with 49.9%. At the other end of the spectrum, there are 6 states reporting 31% or lower, including 2 with less than 30%—Mississippi (26.5%) and Alabama (28.7%). The median full vaccination coverage is 39%, and most states fall between approximately 34-44%.

There are some notable regional disparities as well. The top 6 states in terms of full vaccination coverage are all in the Northeast region. Conversely, the South represents the bottom 6 states and 9 of the bottom 12. Maryland (#9) is the highest-ranking state from the South, although it is among the northernmost states in the region, bordering the Northeast region. New Hampshire is the lowest-ranking state from the Northeast region, although at #22, it is still among the top half of all states. It is also #4 in terms of partial vaccination coverage. The states from the West and Midwest regions are largely scattered throughout the middle of the rankings. While the West represents 3 of the bottom 10 states—Idaho (#42), Utah (#43), and Wyoming (#44)—it also accounts for 2 of the top 10—Hawai’i (#7) and New Mexico (#8).

G20 BACKS VACCINE VOLUNTARY LICENSING On May 21, G20 leaders adopted a declaration pledging to bridge gaps in responses to the COVID-19 pandemic and to support voluntary licensing and technology transfers in order to boost vaccine production. Some view the Rome Declaration, adopted at the conclusion of a special summit on the COVID-19 pandemic hosted by Italy and the European Union's Executive Commission, as a snub to recent international discussions about waiving intellectual property rights for certain COVID-19 vaccines. Instead, G20 leaders reaffirmed their support for patent pooling through the WHO’s ACT-Accelerator, allowing pharmaceutical companies more flexibility in deciding what information to share. While the leaders supported technology pooling, they did not commit to additional financial resources for the scheme, which remains $19 billion short of its goal. Additionally, there are no commitments in the declaration to share vaccine stockpiles with low- and middle-income countries, although it does mention the COVAX facility as a means to do so. The Rome Declaration also lists 16 guiding principles for responding to the current pandemic and preparing for the next.

WORLD HEALTH ASSEMBLY The 74th World Health Assembly opened on May 24 with a focus on ending the COVID-19 pandemic and preparing for the next one. The meeting of the WHO’s decision-making body, this year held virtually, will run through June 1. In his opening remarks, WHO Director-General Dr. Tedros Adhanom Ghebreyesus paid tribute to the more than 100,000 healthcare workers who lost their lives fighting the COVID-19 pandemic on the front lines and called on member states to urgently invest in their health and care workers. Dr. Tedros also warned that no country is “out of the woods” in the pandemic, despite their vaccination rates, saying the pandemic will not end until transmission is controlled in every nation. He urged wealthier countries to help reach a goal of vaccinating at least 10% of the population of every country by September, and a “drive to December” to reach at least 30% by the end of the year. 

In a video message, UN Secretary-General António Guterres laid out a 3-part plan to end the pandemic, calling on nations to more equitably distribute vaccines, diagnostics, and treatments; boost domestic primary health care and universal health coverage; and commit to transforming existing pandemic warning systems, with the WHO at the center of any global preparedness strategy. Member states are expected to receive 3 pandemic-related reports during the meeting, including one from the Independent Panel for Pandemic Preparedness and Response, an independent review of the WHO's Health Emergencies Programme, and a review of how the International Health Regulations have performed during the pandemic.

NOVAVAX VACCINE PHASE 3 TRIAL RESULTS Last week, US pharmaceutical company Novavax posted complete results from a Phase 3 clinical trial testing its 2-dose recombinant protein SARS-CoV-2 vaccine candidate to the preprint server medRxiv, after releasing initial results in March. According to the results of the randomized, double-blind, placebo-controlled study conducted in the United Kingdom, the vaccine, NVX-CoV2373, was 89.7% (95% CI, 80.2-94.6) effective in preventing COVID-19, with no hospitalizations or deaths reported, with post hoc analysis showing efficacies of 96.4% (73.8-99.5) and 86.3% (71.3-93.5) against the original strain and B.1.1.7 variant, respectively. According to some reports, Novavax is expected to apply for emergency authorization in the US in the coming weeks. Notably, the company has never brought a product to market. If it receives authorization, the company has pledged to provide 100 million doses to the US later this year and has promised 1.1 billion doses to COVAX for distribution in low- and middle-income countries. Indian vaccine maker Serum Institute is contracted to make most of the 1.1 billion doses, but backlogs there have Novavax seeking other options. Novavax recently reaffirmed its relationship with the South Korea Ministry of Health and Welfare and SK Bioscience Co. Ltd. to manufacture NVX-CoV2373 and explore expansion of the partnership, having previously entered into a licensing agreement with SK Bioscience to produce 40 million doses of its vaccine candidate. 

Additionally, Novavax announced its participation in a mix-and-match clinical trial testing the potential of 7 SARS-CoV-2 vaccines as booster doses for vaccines from different manufacturers among people who are already fully vaccinated. The company also noted the UK National Health Service, Vaccines Task Force, and National Institute for Health Research are working to ensure participants in the Phase 3 clinical trial who received NVX-CoV2373 are entered into the NHS App, which helps vaccinees prove their vaccination status when traveling. 

MODERNA VACCINE ADOLESCENT CLINICAL TRIAL Moderna announced this week that their SARS-CoV-2 vaccine trial in adolescents, TeenCOVE, has reached its primary endpoint. More than 3,700 adolescents aged 12 to less than 18 years old were enrolled in the trial. No cases of COVID-19 were recorded in vaccine recipients following two doses of the Moderna vaccine. With these results indicating an efficacy of 100% 14 days after both doses, Moderna also found approximately 93% efficacy following one dose of the vaccine. The company plans to send the trial data to regulators in early June. Moderna would be the second SARS-CoV-2 vaccine to be authorized for use in adolescents in the US, following Pfizer-BioNTech’s authorization earlier in May. Both Moderna and Pfizer-BioNTech are investigating vaccine safety and efficacy in children aged 6 months to 11 years, but those results are not expected for some time due to the need to adjust dosing amounts. 

AFRICA COVID-19 MORTALITY People in Africa who become critically ill with COVID-19 are more likely to die than people in other parts of the world, according to a study based on data from 64 hospitals in 10 countries collected between May and December 2020 and published in The Lancet. Among 3,077 critically ill patients admitted to the hospitals—located in Egypt, Ethiopia, Ghana, Kenya, Libya, Malawi, Mozambique, Niger, Nigeria, and South Africa—48.2% died within 30 days, compared with a global average of 31.5%, according to the study. The majority of patients were men (61%), and the overall cohort had an average age of 56 and few underlying conditions. People with pre-existing conditions had the highest risk of poor outcomes. Having chronic kidney disease or HIV/AIDS nearly doubled the risk of death, chronic liver disease more than tripled the risk of death, and diabetes also was associated with poor survival. 

Notably, being male was not associated with increased mortality, an unexpected result, according to the African COVID-19 Critical Care Outcomes Study researchers. They noted this could be due to women having less access to care or biases in care when critically ill. Overall, the researchers posited scarce critical care resources and under-resourced facilities could have played a role in the deaths, as well as an apparent failure to use available resources and medical interventions. The researchers highlighted limitations to their study, including that the observations occurred primarily at university-affiliated, government-funded, and tertiary hospitals, so outcomes could be worse in lower-level, less-resourced hospitals across the continent. Another analysis published in The Lancet found that Africa’s second COVID-19 wave was more severe than the first. Taken together, these studies underscore the importance of improved epidemiological surveillance on the continent. 

RESPIRATORY STATUS & MORTALITY RISK Researchers from the University of Washington and Rush University Medical Center (Illinois; US) found that respiratory symptoms may not be an accurate predictor of COVID-19 mortality risk. The presence of respiratory symptoms—such as coughing, wheezing, or difficulty breathing—may not necessarily correlate with respiratory compromise. Clinical measurements such as blood oxygen saturation and respiratory rate can provide a more objective assessment of respiratory compromise. The researchers evaluated data from more than 1,000 hospitalized COVID-19 patients and assessed COVID-19 mortality risk associated with both respiratory symptoms as well as oxygen saturation and respiratory rate.

The researchers found that blood oxygen saturation of 91% or lower was significantly associated with increased risk of COVID-19 mortality (compared to 92% or higher), ranging from 1.8 times the risk for 89-91% to 4.0 for less than 80%. Increased respiratory rate was also significantly associated with increased mortality. The risk of death was 1.9 times higher among individuals with respiratory rates of 23-24 breaths per minute (compared to 20 or fewer). Individuals with more than 32 breaths per minute were 3.2 times as likely to die. In contrast, the presence of respiratory symptoms or fever were not significantly associated with increased COVID-19 mortality.

LONG-TERM EFFECTS IN CHILDREN Most children with COVID-19 who develop a rare but potentially severe condition known as multisystem inflammatory syndrome in children (MIS-C) experience symptom alleviation within 6 months, according to a small study published May 24 in The Lancet Child & Adolescent Health. Researchers followed 46 children initially admitted with COVID-19-related MIS-C—also known as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2—to Great Ormond Street Hospital (London; UK) between April 4 and September 1, 2020. Six months after discharge from the hospital, only 1 child still had systemic inflammation, 2 had heart abnormalities, and 6 had gastrointestinal symptoms. Eighteen of the children continued to have diminished exercise tolerance and 15 were experiencing emotional difficulties. The researchers emphasized that longer-term follow-up studies are needed to better characterize the natural history of MIS-C among children with COVID-19.

US COVID-19 EPIDEMIC IN UNVACCINATED INDIVIDUALS A report from The Washington Post breaks down national and state populations into vaccinated and unvaccinated individuals by assuming that all vaccinated individuals are fully immune and removes them from the population. While this is not necessarily the case, we expect this to be a reasonable approximation due to the low risk of breakthrough infection—and even lower risk for severe disease and death. With just the unvaccinated portion of the population remaining, the report estimates the per capita COVID-19 daily incidence, hospitalization, and mortality among unvaccinated individuals. 

While the overall daily incidence is declining across the country, the Washington Post analysis says that COVID-19 “is spreading as fast among the unvaccinated as it did during the winter surge.” There are just fewer susceptible individuals due to vaccination. Similar trends are apparent for both hospitalizations and mortality. While nearly half of the US population has received at least 1 dose and nearly 40% are fully vaccinated, unvaccinated individuals remain at risk, and vaccination coverage is not yet sufficient to provide protection to the unvaccinated portion of the population. Vaccination coverage varies widely by state, and states with lower coverage still have substantial populations remaining to facilitate community transmission if effective protective measures are not in place.

CLINICAL TRIAL LANDSCAPE Since the beginning of the pandemic, many studies testing potential COVID-19 therapies have been too small to gather meaningful data or did not include a control arm. Researchers in Europe and the US are working to launch large-scale, randomized clinical trials of multiple drugs to evaluate whether they work to help people with COVID-19 are more likely to survivor or recover more quickly. The WHO is relaunching its multi-arm Solidarity trial to look at repurposed drugs meant to prevent immune system overreaction in COVID-19 patients, and the REMAP-CAP study is ongoing in Europe. In the US, the NIH-sponsored Accelerating COVID-19 Therapies and Vaccines (ACTIV) program is set to begin enrolling patients in ACTIV-6, a master protocol that will evaluate at least 4 different oral medications already approved to treat other diseases among people with mild to moderate COVID-19 who are not hospitalized. These trials are all designed to examine several treatment options simultaneously and efficiently, with built-in flexibilities and pooled control groups. The FDA recently released new guidance for these types of master protocols. One potential obstacle for these larger studies is enrolling sufficient numbers of patients, as some places are experiencing sustained declines in new COVID-19 cases.

SARS-COV-2 ORIGINS Many questions remain regarding the origin of the SARS-CoV-2 virus. An article in the The Wall Street Journal (WSJ) says that 3 illnesses among personnel who worked at the Wuhan Institute of Virology (WIV; China) in November 2019 are linked to the COVID-19 pandemic. Reportedly, the individuals’ symptoms were consistent with COVID-19; however, COVID-19 shares many common symptoms with other diseases, including seasonal influenza. The illnesses were previously listed in a fact sheet issued by the US Department of State, but the WSJ article indicates that additional details—including the number of cases and the timing of the illnesses—are contained in an “undisclosed U.S. intelligence report.” The WSJ article acknowledges that some government officials familiar with the intelligence report question the “supporting evidence for the assessment,” and to our knowledge, the report’s contents have not been released publicly. In a separate article, WSJ also investigated a potential link between illnesses at a Chinese mine in 2012 and the emergence of SARS-CoV-2 in 2019.

As we have covered previously, it will be difficult to definitively determine the original source of SARS-CoV-2, whether from a natural spillover event, laboratory accident, or other events. Continued discussions about the possibility of a laboratory release has fueled calls for further investigations into activities at WIV. A previous investigation led by the WHO determined that the likelihood of the pandemic originating from a laboratory release to be “extremely low,” but in the absence of definitive evidence of another source, it is nearly impossible to rule it out. Rigorous, transparent, and independent investigations are an important step to understanding the origins of the pandemic, but myriad technical, practical, and political barriers remain that could impede these efforts.

OLYMPICS With the 2020 Summer Olympic Games scheduled to begin in July, Japan continues to combat one of its largest COVID-19 surges. Officials from hospitals in Osaka, Japan’s second largest city, are warning that the medical system could be on the verge of collapse. Some experts and health officials worry that the influx of tens of thousands of Olympic participants will further strain the already overburdened health system and potentially introduce new variants of concern into the population. The Japanese government recently opened 2 mass vaccination centers following Prime Minister Yoshihide Suga’s pledge to vaccinate the country’s entire elderly population of 36 million citizens by the end of July. Still, vaccination levels remain extremely low, with only around 2% of the population fully vaccinated.

In response to Japan’s ongoing surge, the US Department of State recently upgraded its travel advisory from a Level 3 (Reconsider Travel) to Level 4 (Do Not Travel). The US CDC also stated that even vaccinated travelers could be at risk of contracting and spreading SARS-CoV-2 due to the circulation of variants of concern. Notably, international spectators will not be permitted to attend the Olympics, but it is unclear if or how the Level 4 travel advisory could impact athletes’ travel from the US or other nations that consider US guidance.