EPI UPDATE The WHO COVID-19 Dashboard reports 104.37 million cases and 2.27 million deaths as of 11am EST on February 5.
Our World in Data reports that 119.48 million vaccine doses have been administered globally, a 65% increase since this time last week.
According to data compiled by Our World in Data, at least 65 countries have initiated SARS-CoV-2 vaccination campaigns. The majority of these countries are in Europe and North America, although vaccination efforts are starting in Africa, South America, South and Southeast Asia, and the Eastern Mediterranean region. In terms of total doses administered, the US is #1 globally (35.2 million), followed by China (31.2 million), the UK (11.0 million), Israel (5.3 million), and India (5.0 million). In total, 15 countries have administered 1 million or more vaccine doses, and 42 have administered more than 100,000.
Because some individuals have only received the first dose while others have received both, it is difficult to determine the proportion of a country’s population with full coverage. The doses administered per capita, however, can provide insight into the progress toward full coverage. Full coverage with 2 doses would correspond to 200 doses per 100 population, so with that in mind, we can estimate the proportion of those doses that each country has administered so far. On a per capita basis, Israel is #1 globally with 61.7 doses administered per 100 population, which corresponds to approximately 30.8% of its way toward full coverage. The United Arab Emirates (UAE) is #2 with 34.8 doses per 100 population (19.5%), followed by Seychelles (37.7; 18.9%), the UK (16.2; 8.1%), and the US (10.6; 5.3%).
Broken down by continent, Asian countries have reported the most cumulative doses administered, with 49.77 million. Asia is followed by North America (36.98 million), Europe (28.44 million), South America (3.82 million), and Africa (390,160). In Asia (including the Eastern Mediterranean region), China represents the majority (64.2%) of the doses administered, which is not surprising, considering that it initiated vaccination months before most other countries. China is followed by Israel (10.7%), India (10.0%), the United Arab Emirates (7.7%), and Turkey (5.0%). The North American total is driven principally by the US, which is reporting more than 95% of the administered doses. Canada, Costa Rica, Mexico, and Panama have also started vaccinations. Similarly, Brazil is driving the South American total, with more than 80% of the administered doses. Brazil is followed by Argentina (11.6%) and Chile (7.6%). In Europe, the doses the UK accounts for slightly less than 40% of the total, followed by Germany (10.5%), Italy (8.2%), Spain (6.7%), and France (6.6%). Data are only available for 4 African countries—Algeria, Egypt, Morocco, and Seychelles. Morocco has reported approximately 90% of the doses administered, followed by Seychelles with 10%.
UNITED STATES
The US CDC reported 26.40 million total cases and 449,020 deaths. The daily incidence continues to fall, down to 134,523 new cases per day—a 46% decrease from the peak on January 8 (248,706). The daily mortality continues to decrease as well. The US is currently averaging 3,056 deaths per day, a decrease of 8% since January 26 (3,316). The US will almost certainly surpass 450,000 cumulative deaths in this afternoon’s update:
1 death to 50k- 55 days
50k to 100k- 33 days
100k to 150k- 63 days
150k to 200k- 55 days
200k to 250k- 58 days
250k to 300k- 25 days
300k to 350k- 20 days
350k to 400k- 16 days
400k to 450k- 16 days
US Vaccination Effort
The US CDC reported 57.49 million vaccine doses distributed and 35.20 million doses administered. The US has administered 61.2% of the distributed doses, which is a slight decrease from Tuesday (64.5%). In total, 27.91 million people (approximately 8.5% of the US population) have received at least 1 dose of the vaccine, and 6.93 million (2.1%) have received both doses. The average daily doses administered fell sharply over the past several days, down from a high of 1.4 million doses per day on January 30 to 892,946 on February 3, a decrease of 36%. The breakdown of doses by manufacturer remains relatively even, with slightly more Pfizer-BioNTech doses administered (18.84 million; 54%) than Moderna (16.26 million; 46%).
A total of 4.21 million doses have been administered at long-term care facilities (LTCFs) through the Federal Pharmacy Partnership for Long-term Care (LTC) Program*, including residents and staff. This covers 3.40 million individuals with at least 1 dose and 796,324 with 2 doses. Approximately 60% of the doses have gone to residents and 40% to staff.
*The dashboard only includes data for doses administered through the federal program. It does not report data from West Virginia, which opted out of the program.
PANDEMIC FORECASTING In the White House’s National Strategy for the COVID-19 Response and Pandemic Preparedness, published in January, US President Joe Biden included the need for a National Center for Epidemic Forecasting and Outbreak Analytics “to modernize global early warning and trigger systems to prevent, detect, and respond to biological threats.” Under current systems, there are limited federal resources for epidemiological modeling, and independent disease modelers, including from academic institutions and private sector think tanks across the country, are often called upon to support the government’s preparedness and response efforts, typically as volunteers. Dr. Caitlin Rivers, from the Johns Hopkins Center for Health Security, and Dr. Dylan George, Vice President of In-Q-Tel, have advocated for this capacity for years, and the US government has finally heeded their call for action. President Biden directed federal agencies to develop plans to establish the center in an executive order issued on his second day in office.
The National Center for Epidemic Forecasting and Outbreak Analytics would provide a service similar to weather forecasting, except for endemic and epidemic diseases. COVID-19 will certainly not be the last major disease threat we face, and epidemiological and statistical analysis will be critical to rapidly identifying the emergence of outbreaks and epidemics and providing elected and health officials with the information needed to identify, implement, and adapt appropriate response activities. Funding under the proposed American Rescue Plan would support expanded testing and analytic capabilities during the COVID-19 response, including for genomic sequencing to address the threat of emerging variants, but longer-term investment is needed to embed the type of analytic capacity in the federal government, where it can inform national policy and response to epidemic events.
VACCINATION DOSE SCHEDULE & TRANSMISSION RISK
A study (preprint for The Lancet) of data from the Phase 3 clinical trials of the AstraZeneca-Oxford University vaccine evaluated vaccine efficacy after a single dose and for alternate timing for the booster dose. Notably, the UK adapted the timing for the booster dose from 4 weeks after the first dose—which is how the vaccine was designed to be administered and the timing used for clinical trials—to 12 weeks in an effort to provide the first dose to as many people as possible. This study assessed the vaccine’s efficacy in participants who received the 2 doses between 4 and 12 weeks apart.
The researchers found that the efficacy after the first dose did not wane in the first 12 weeks. A single dose of the vaccine was 76% efficacious in preventing symptomatic COVID-19 disease in the first 90 days after vaccination, although it was associated with a substantial decrease in efficacy with respect to preventing asymptomatic infection. Notably, however, the additional asymptomatic infections could potentially be among participants who would have otherwise developed COVID-19 symptoms. Additionally, the efficacy in preventing symptomatic disease was higher in participants who received the booster dose later than in those who received it earlier. Vaccine efficacy was 82.4% among participants who received their booster dose 12 weeks or longer after the first dose, compared to 54.9% in those who received their 2 doses less than 6 weeks apart. These results provide support for vaccination plans that delay the booster dose beyond the intended 4 weeks, considering that the immunity conferred after the first dose appears to be relatively stable over the first several months and the overall protection appears to increase with an increased time between the prime and booster doses.
J&J EUA SUBMISSION Yesterday, Johnson & Johnson (J&J) submitted an application to the US FDA for an Emergency Use Authorization (EUA) for its SARS-CoV-2 vaccine, developed in collaboration with Janssen Biotech. The US FDA announced that it will review the submission over the coming weeks, and it will convene a meeting of its Vaccines and Related Biological Products Advisory Committee (VRBPAC) on February 26 to discuss the vaccine’s safety and efficacy data. The FDA did not commit to a timeline for ruling on the EUA submission; however, it will “review the request as expeditiously as possible” following the VRBPAC meeting. As with the previous vaccines, the FDA intends to publish relevant data in the days prior to the VRBPAC meeting. J&J announced interim results from the Phase 3 clinical trials in a press release issued on January 29, but the full dataset or final analyses have not yet been released publicly or subjected to peer review. In addition to the US FDA, J&J intends to submit an application for a Conditional Marketing Authorisation (CMA) to the European Medicines Agency “in the coming weeks.”
J&J’s most recent press release indicates that it expects to be able to begin shipping vaccine doses “immediately following authorization.” The company expects to provide 100 million doses by mid-2021, but it did not indicate how much is currently available. Multiple news media reports indicate that the initial supply is expected to be relatively low. The J&J-Janssen vaccine utilizes a single dose, which provides an advantage over existing vaccines in terms of the potential to speed vaccination operations. And while the J&J-Janssen vaccine does require moderately low freezing temperatures (-4°F; -20°C) for long-term storage, it can be stored for up to 3 months at normal refrigeration temperatures (6°F–46°F; 2°-8°C), which could facilitate distribution and on-site storage at vaccination clinics.
COVAX VACCINE ALLOCATION On February 3, Gavi published interim SARS-CoV-2 vaccine allocation for the COVAX facility. The interim plan includes estimated quantities and timeline for vaccine distribution of the Pfizer-BioNTech and AstraZeneca-Oxford University vaccines to low- and middle-income countries eligible to receive doses through the COVAX effort. As we have covered previously, COVAX is a multilateral program to pool funding in an effort to help lower-income countries compete against wealthier countries in terms of purchasing doses of SARS-CoV-2 vaccines. In total, the interim plan estimates that 336 million doses of the AstraZeneca-Oxford vaccine and 1.2 million doses of the Pfizer-BioNTech vaccine will be distributed in the first half of 2021.
Due to the ultra-cold temperatures required for the Pfizer-BioNTech vaccine, those doses were only allocated to countries that requested early delivery of that vaccine and were determined to be capable of maintaining the cold chain. The available inventory was distributed relatively evenly across the eligible countries, with the aim of achieving full coverage for at least 3% of the population for each country in order to provide protection for the most vulnerable individuals (eg, healthcare workers). On average, the national allocations cover 3.3% of the countries' respective populations.
Of the 190 eligible countries, 145 are included in the earliest round of vaccine allocations, and delivery is expected to begin as early as late February and progress through the first half of 2021. The estimates aim to provide countries with an approximate quantity of doses in order to enable them to implement more concrete plans for national vaccine distribution and administration logistics and operations. The interim guidance notes that the AstraZeneca-Oxford vaccine has not yet received an Emergency Use Listing (EUL) from the WHO, but that evaluation process is in progress.
SARS-CoV-2 TRANSMISSION The scientific community is still uncovering the full picture of SARS-CoV-2 transmission dynamics. A study published in The Lancet: Infectious Diseases analyzed SARS-CoV-2 transmission among clusters in Catalonia, Spain, to understand the relationship between viral load and transmission risk. The researchers utilized participant data from a previous clinical trial, and they identified 314 COVID-19 patients that met their inclusion criteria. Among those patients, 282 had at least 1 contact (753 total contacts). The index patients infected 125 secondary cases, corresponding to a secondary attack rate of 17%. The researchers identified a statistically significant association between viral load in the index patients and the subsequent secondary attack rate. Among index patients with the lowest viral load, index patients exhibited a secondary attack rate of 12%, compared to 24% among the highest group. The researchers estimate that the odds of secondary transmission increase 30% for every log(10) increase in viral load. Additionally, the study found increased likelihood that secondary cases would develop COVID-19 symptoms associated with increased viral load in the index patients (aHR of 1.12 per log(10) increase in viral load). While further research is needed to more fully characterize the factors associated with transmission, this study provides evidence that the index patient’s viral load could be a major driver of secondary transmission risk and potentially disease severity in secondary cases.
An editorial published in Nature discusses the need to shift focus away from surface decontamination as a mechanism to reduce SARS-CoV-2 transmission risk. Multiple studies have found that transmission of SARS-CoV-2 via contaminated surfaces, or fomites, is relatively rare compared to respiratory transmission via droplets or aerosols. Despite the evidence supporting respiratory exposure as the overwhelming driver of community transmission, numerous public health entities, including the WHO and US CDC, continue to emphasize the importance of surface decontamination, which can cause confusion among the public regarding transmission risk and appropriate protective measures. Notably, surface decontamination efforts, while highly visible and easy to recognize, are costly and likely not effective means of reducing transmission risk. The editorial calls for increased focus on improving ventilation and air filtration capacity to reduce respiratory exposure. Additionally, proper physical distancing and face mask use remain key tools in mitigating exposure and transmission risk for individuals.
GSK-CUREVAC VACCINE CANDIDATE GlaxoSmithKline (GSK) announced a partnership with German biotech company CureVac to develop a new, multivalent SARS-CoV-2 vaccine and manufacture CureVac’s first generation vaccine candidate. The joint vaccine development effort aims to target emerging SARS-CoV-2 variants, with the goal of making a product available in 2022. Under the new agreement, GSK will also manufacture up to 100 million doses of CureVac’s existing vaccine candidate in 2021, which is currently in Phase 2b/3 clinical trials in Europe and Latin America. Interim data from the ongoing trials are expected sometime in the first quarter of 2021.
TAIWAN VACCINATION The Taiwanese government is preparing for its national SARS-CoV-2 vaccination effort, but the source of its doses remains uncertain. Like many countries, Taiwan is currently awaiting delivery for doses it purchased months ago from multiple sources. Taiwan has largely managed to contain COVID-19, but health officials are responding to its first outbreak in months. Notably, Taiwan did not report a single domestic case between April 2020 and January 2021. Multiple Taiwanese vaccine candidates are in clinical trials, but the most advanced have not yet completed Phase 2 trials. The Taiwanese government has taken multiple approaches to securing vaccines, including COVAX facility led by the WHO and Gavi. Reportedly, Taiwan is experiencing problems obtaining doses from Western countries, potentially as a result of opposition by the Chinese government. Taiwan’s Minister of Health has reportedly expressed opposition to importing SARS-CoV-2 vaccines developed in China, due in part to an existing policy that prohibits importing vaccines and other “biological products” from China. Additionally, there is some uncertainty regarding the vaccines’ efficacy and safety data.
Notably, the interim COVAX allocation plan published by Gavi indicates that 1.3 million doses of the AstraZeneca-Oxford vaccine will be allocated to non-UN member states, potentially including Taiwan; however, the final determination will not be made until after the WHO issues an Emergency Use Listing (EUL). There is resistance to import Chinese made vaccines due to policies the shipment of biological products from China. In an effort to contain the ongoing outbreak in the absence of a vaccine, Taiwan is placing as many as 5,000 at-risk individuals into quarantine.
MYANMAR PROTESTS Following Monday’s military coup d’etat in Myanmar, staff from more than 70 hospitals and medical departments across 30 towns have stopped work in protest. Protesting healthcare workers are wearing red ribbons, and the Myanmar Civil Disobedience Movement issued a statement on February 3 indicating that they will not work for the new military government. According to one doctor, many who volunteered to support the COVID-19 response did so were inspired by Aung San Suu Kyi, leader of Myanmar’s National League for Democracy, who was deposed during the coup. The protest by healthcare workers has raised concerns about Myanmar’s new vaccination campaign, which started in late January, just days before the coup.
EASTERN MEDITERRANEAN REGION Earlier this week, a number of countries in the Eastern Mediterranean region announced new COVID-19 restrictions. For the most part, the Eastern Mediterranean region has avoided high COVID-19 mortality experienced by countries in other parts of the world, but recent increases in daily incidence prompted concerns about another COVID-19 surge. In response to the increasing transmission, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates implemented new restrictions on gatherings, including in public and at events like weddings and funerals; the operations of businesses, including retail stores and shopping malls, restaurants and bars, gyms and fitness centers; and international travel. Additionally, Kuwait is prohibiting celebrations for its National Day holiday on February 25. The duration of the measures varies by country, ranging from 10 days to several weeks.
The trial will initially involve the Pfizer-BioNTech and AstraZeneca-Oxford University vaccines. The vaccines utilize different technology, with the Pfizer-BioNTech vaccine using an mRNA platform and the AstraZeneca-Oxford vaccine using an adenovirus platform. The participants will be divided among 8 trial arms. Four (4) will be control groups, which will receive 2 doses of the same vaccine (2 groups per vaccine) either 4 or 12 weeks apart. The other 4 groups will trial the mixed doses, with 2 groups receiving the AstraZeneca-Oxford dose first followed by the Pfizer-BioNTech dose, administered either 4 or 12 weeks apart, and 2 groups receiving the doses in the opposite order (4 or 12 weeks apart). The UK announcement stated that additional combinations could be added later, as additional vaccines received authorization.
US PHARMACY VACCINATIONS On February 2, the White House announced that the US government will increase distribution of SARS-CoV-2 vaccine doses nationwide. The principal increase will be in the form of 1 million doses per week that will be distributed to approximately 6,500 retail pharmacies nationwide, including major chains such as CVS, Rite Aid, and Walgreens. The pharmacies will make vaccination available to eligible individuals free of charge, which will dramatically increase the number of locations in the community where individuals can get vaccinated. The plan aims to scale up the number of participating pharmacies to 40,000 locations across the country.
Notably, the allocation for pharmacies will be in addition to the doses already distributed to states, and the state allotment will also increase by 500,000 doses per week, up to 10.5 million doses per week nationally. The initial pharmacy locations were deliberately selected to improve equitable access for “socially vulnerable communities” that are at elevated risk for infection and severe disease, including racial and ethnic minorities. Many pharmacies are already supporting vaccination operations in collaboration with state and local governments, but the new program will distribute the doses directly to pharmacies.
EMERGING VARIANTS & TESTING The emergence of new SARS-CoV-2 variants, particularly those that appear to be more transmissible and/or could mitigate the efficacy of vaccines or therapeutics, and expanded access to vaccination are raising concerns regarding the accuracy of existing tests. A team of researchers from the Johns Hopkins Center for Health Security developed an overview of diagnostic testing accuracy for these new variants as well as an insight into the potential effects of vaccination on diagnostic and serological testing.
The molecular diagnostic tests widely in use for SARS-CoV-2 detect infections by targeting specific genetic sequences present in the virus. In fact, a specific type of failure for these tests—an S-gene (spike protein) target failure—was instrumental in first detecting the B.1.1.7 variant. Both the B.1.1.7 and 501Y.V2 (B.1.351) variants have mutations on the spike protein; however, most existing test kits target other sets of genes. The majority of tests are expected to remain effective in detecting infection with the new variants, and the US FDA has issued a warning for those tests that utilize genetic sequences for the spike protein. Most of the existing diagnostic tests are capable of detecting infection with the known emerging variants; however, their sensitivity could be affected for future variants, depending on the specific mutations involved.
Vaccination is not expected to result in positive diagnostic tests. While both of the vaccines currently authorized for use in the US—the products from Pfizer-BioNTech and Moderna—both include mRNA corresponding to the spike protein, the quantity of mRNA in each dose is very small, much less than is generated during SARS-CoV-2 infection, and it does not amplify like the virus would. As we noted above, most diagnostic tests target other portions of the SARS-CoV-2 genome, and in combination with low quantity of mRNA, it is unlikely that an individual would test positive due to the vaccine. On the other hand, serological tests after vaccination could yield either positive or negative results, depending on the test. Serological tests identify the presence of antibodies as an indication of prior infection; however, the specific antibodies vary by test. The Pfizer/BioNTech and Moderna vaccines generate antibodies against the spike protein, so only serological tests that target those antibodies would yield positive results after vaccination. Conversely, tests that target antibodies against other parts of the virus (eg, receptor binding domain) would not identify the antibodies induced by the vaccine or provide any indication if the vaccine successfully generated an immune response.
2020 OLYMPICS The International Olympic Committee (IOC), International Paralympic Committee (IPC), and the Tokyo 2020 Organising Committee published the first in a series of “playbooks” that will outline protective measures that will be put in place during the 2020 Olympic and Paralympic Games* in Tokyo, Japan—currently scheduled for July-August 2021. Each playbook will focus on a specific stakeholder group, including the international federations, press, broadcasters, and athletes and officials. The playbook for athletes and officials has not yet been published; however, multiple media reports indicate that there will be testing requirements for athletes, both before arrival and regularly during their stay, and athletes will be directed to return home after they are done competing. Additionally, there could be a prohibition on physical contact between athletes outside of competition.
*The 2020 Olympic and Paralympic Games will retain their 2020 designation, even though they will be held in 2021.
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