EPI UPDATE The WHO COVID-19 Dashboard reports 84.23 million cases and 1.84 million deaths as of 4:00am EST on January 5. Over the past 2 weeks, the WHO reported decreased global weekly incidence and mortality compared to the week of December 14, potentially a result of reporting delays over the 2 holiday weekends. The global cumulative incidence surpassed 80 million cases on December 29. From the first reported COVID-19 case, it took 177 days to reach 10 million cases. From there:
10 to 20 million- 44 days
20 to 30 million- 37 days
30 to 40 million- 31 days
40 to 50 million- 21 days
50 to 60 million- 17 days
60 to 70 million- 17 days
70 to 80 million- 16 days
The global cumulative mortality surpassed 1.75 million deaths on December 27. From the first reported death, it took 115 days to reach 250,000 deaths. From there:
250k to 500k- 56 days
500k to 750k- 46 days
750k to 1 million- 45 days
1 to 1.25 million- 40 days
1.25 to 1.5 million- 26 days
1.5 to 1.75 million- 23 days
On December 26, the US surpassed 330,000 cumulative COVID-19 deaths, which equates to approximately 1 death for every 1,000 people nationwide. The US is not the first country to reach this milestone, but it is certainly the largest in terms of population. To date, only 18 countries have reported per capita cumulative mortality greater than 1 death per 1,000 population. All but 2 of these countries are located in Europe, with the exceptions being Peru (1.15) and the US (1.07). More than half of these countries have populations less than 10 million, including 4 with fewer than 1 million people. San Marino—with a population of fewer than 34,000—is #1 globally, with 1.83 deaths per 1,000 population. Notably, Belgium (population 11.6 million) is close behind at 1.70. Slovenia is #3 with 1.37 deaths per million.
The trends in cumulative incidence among the European countries are very similar over the course of the pandemic, whereas Peru and the US exhibit different trajectories. In Europe, countries that were severely affected early in the pandemic have steep initial curves, which began to level off in May. The cumulative mortality curves for most of the European countries, regardless of whether they were severely affected during Europe’s “first wave,” were relatively flat over the summer before sharp increases starting in September-October, corresponding to Europe’s second wave. In contrast, Peru’s cumulative mortality curve increased steadily through approximately August, at the height of South America’s first wave, and has tapered off since that time. The United States’ initial sharp increase in March-April, during the initial COVID-19 surge, was less pronounced than many European countries; however, when Europe brought its COVID-19 epidemic over the summer under control, COVID-19 mortality in the US continued to grow steadily during its summer resurgence. US mortality rate then increased again in November, corresponding to the autumn/winter surge.
UNITED STATES
The US CDC reported 20.56 million total cases and 350,664 deaths. The US reported a new single-day record incidence of 284,554 new cases on January 3, becoming the first country to report more than 250,000 new cases in a single day. The US surpassed 20 million cumulative cases on January 2. From the first case reported in the US, it took 200 days to reach 5 million cases. From there:
5 million to 10 million- 92 days
10 million to 15 million- 29 days
15 million to 20 million- 24 days
The US surpassed 325,000 cumulative deaths on December 23 and 350,000 deaths on January 4. The 9 days to increase from 300,000 to 325,000 deaths matched the rate at the peak of the initial surge in March. Notably, the 12 days between 325,000 and 350,000 included 2 major holiday weekends, which likely delayed reporting to some extent. From the first US death, it took 55 days to reach 50,000 deaths. From there:
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
As a reminder, it may be difficult to track national-level epidemiological trends in the US over the coming weeks. Reporting delays over the Christmas and New Year’s holiday weekends, and associated catch-up reporting, could obscure epidemiological trends, including the effects of holiday travel and gatherings as far back as Thanksgiving.
While many of the metrics we track vary considerably over holiday weekends, hospitalizations tend to remain relatively consistent. Analysis reported by the COVID Tracking Project shows a 4.6% increase in hospitalizations for the last week of 2020, compared to the previous week. The number of nationwide hospitalizations does appear to be tapering off to some degree, but the US continues to set new records, now more than double the number of hospitalized COVID-19 patients reported at the height of the previous 2 peaks. Hospitalization trends vary by region, as the US epidemic shifts away from the Midwest, which was most severely affected in the earlier part of the autumn/winter surge. States in the South and West regions continue to report increasing hospitalizations, including new records in the South. Hospitalizations in the Midwest peaked in late November/early December and are now steadily decreasing, and Northeastern states appear to be approaching a second peak. While the raw totals vary widely by region, the per capita hospitalizations are actually relatively even, with all 4 regions falling between 310 and 410 hospitalizations per million population. In total, 6 states are reporting more than 500 hospitalizations per million population: Alabama (628), Arizona (659), California (560), Georgia (530), Nevada (632), and Tennessee (508). Only 2 states, Hawai’i (60) and Vermont (66), and Guam (68) are reporting fewer than 100 hospitalizations per million.
VACCINE AUTHORIZATIONS Considerable progress has been made over the past several weeks in terms of regulatory agencies authorizing the use of SARS-CoV-2 vaccines, including several new vaccines that had not previously been authorized for use anywhere. Following the US emergency authorization of the Moderna vaccine, Health Canada authorized the Moderna vaccine for use among the public. Canada is the second country to authorize the Moderna vaccine, and this is the second vaccine authorized for use in Canada. Additionally, the WHO issued its first Emergency Use Listing (EUL) for a SARS-CoV-2 vaccine for the Pfizer/BioNTech version. An EUL from the WHO can help expedite regulatory review and authorization in countries around the world, and it “enables UNICEF and the Pan-American Health Organization [PAHO] to procure the vaccine for distribution to countries in need.”
Additionally, India issued an emergency authorization for the vaccine developed by Bharat Biotech, an Indian pharmaceutical company, that appears to still be in the middle of Phase 3 clinical trials. Reportedly, the absence of publicly available Phase 3 trial data for the AstraZeneca/Oxford and Bharat Biotech vaccines and a lack of transparency regarding the conduct of those trials has prompted criticism from health experts in India, following the authorization of the two vaccines.
US VACCINATION The rollout of the United States’ SARS-CoV-2 vaccination program has faced a number of challenges. While the federal government is responsible for procuring and distributing the vaccine, public health and healthcare in the US are largely controlled at the state level. According to US CDC data, more than 15 million total doses have been distributed nationwide; however, only 4.5 million (29.5%) have been reported as administered. This total includes 2.5 million doses distributed for use at long-term care facilities (LTCFs), of which only 365,000 (14.4%) have been administered. While distribution to states is relatively balanced nationwide, on a per capita basis, the speed at which states are administering the vaccines varies widely.
Delays in administering vaccines in several states have received significant media coverage. In Florida, for example, images and videos show older adults, many in wheelchairs, waiting in long lines to receive their vaccines, including some who waited outside overnight for the opportunity to be vaccinated. In Florida, local governments are responsible for implementing mass vaccination programs, including mechanisms to schedule appointments and allocate doses to appropriate populations, and differences in their approaches have impacted mass vaccination operations. States also vary in terms of who is eligible for vaccination, including who gets priority among the highest tier groups. In some states, such as New York, healthcare workers in primary care or outpatient settings were not among the initial priority for eligibility, but eligibility was expanded this week to include them. Many health professionals and experts have noted challenges that primary care clinicians are facing in terms of getting vaccinated, particularly considering their risk of exposure to patients with milder symptoms or who are seeking testing. Other states, such as Louisiana, are expanding beyond the federal Tier 1a recommendations to include all adults aged 70 years and older.
In some states, delays in administering the allocated vaccine doses have prompted stern responses from state officials. In Florida, Governor Ron DeSantis threatened to withhold future allotments from hospitals that do not increase the pace of their vaccinations. Similarly, New York Governor Andrew Cuomo indicated that he would hold back future doses and potentially impose substantial fines for hospitals that do not administer their allocated doses by the end of this week. One of the challenges affecting hospitals’ ability to administer their vaccines is opacity in the national allocation and delivery process. States may not know how many doses they will receive until days before the delivery arrives, so governments and hospitals may be unwilling to administer their entire inventory to ensure they have enough on hand to cover the second doses. Until state and local governments and health systems can gain confidence in the delivery volume and timeline, we could continue to observe lower vaccination rates in many locations.
EU VACCINATION European countries began initiating their mass vaccination efforts against SARS-CoV-2 on December 26. As of now, only the Pfizer/BioNTech vaccine is authorized for use in Europe; however, other vaccines are currently under evaluation by the European Medicines Agency (EMA), including ongoing assessments regarding emergency authorization for the Moderna vaccine, which has already been issued an Emergency Use Authorization (EUA) by the US FDA. As of today, EU countries have administered more than 900,000 doses of the vaccine, led by Germany, which has administered the first dose to nearly 317,000 individuals.
ISRAEL VACCINATION Israel appears to be leading all other countries in terms of its mass vaccination program. Since commencing vaccination operations on December 19, Israel has administered more than 1 million doses nationwide, covering more than 10% of its population. For comparison, the US has administered 4.56 million doses; however, on a per capita basis, Israel (14.14 doses per hundred population) is exceeding #2 Bahrain (3.62) by a factor of 4 and the UK (#3; 1.39) and US (#4; 1.38) by a factor of 10. Reportedly, Israel is administering more than 150,000 vaccinations per day. While this pace could enable Israel to cover 100% of its population (9 million) within 2 months, progress on administering the first doses will largely pause from January 10-31 to begin administering second doses. Israel is currently only using the Pfizer vaccine, but it expects to receive its first doses of the Moderna vaccine in March.
UK VACCINATION TIMING In an effort to increase the number of people with some degree of protection against SARS-CoV-2, the UK government announced that it is increasing the time between the first and second dose of SARS-CoV-2 vaccines to 4 months, for both the Pfizer/BioNTech and AstraZeneca vaccines. The policy will be implemented across all 4 UK countries based on advice from the UK’s Joint Committee on Vaccination and Immunisation (JCVI). This decision increases the time before individuals can be fully vaccinated against SARS-CoV-2; however, it allows the UK government to use its available vaccine doses to provide the first dose to more people, which can provide them with a lower degree of protection.
Some health experts, including multiple professional associations in the UK, have expressed opposition and concern about the decision, noting that the vaccines were not necessarily designed to be administered in this manner, and the clinical trials did not explicitly evaluate the degree or duration of protection conferred through partial vaccination. The concerns include a lower degree of protection from a single dose, waning immunity after 21 days, and the potential that partial immunity could contribute to the emergence of vaccine-resistant strains of the virus. The UK’s Chief Medical Officers defended the policy by citing the need to provide protection to as many people as possible, even if it is not the full degree of protection offered by the full vaccination. They argue that the first dose accounts for “the majority of the initial protection” and that the second dose contributes more to the duration of immunity. Notably, Pfizer issued a statement indicating that its clinical trials did not provide data on the level of protection conferred by the first dose beyond 21 days. The US FDA issued a statement yesterday indicating that the US would not follow the UK’s lead and would, instead, continue to administer the second vaccine doses at the “specified intervals,” 3 weeks for the Pfizer/BioNTech vaccine and 4 weeks for the Moderna vaccine.
VACCINE PHASE 3 CLINICAL TRIALS While a small selection of vaccines have gone through clinical trials and are conditionally approved for use, other vaccines are still under investigation and going through the clinical trials process. The vaccine candidate developed by Novavax recently entered Phase 3 clinical trials. The participants will be grouped into 2 cohorts, one aged 18-64 years and the other for individuals aged 65 years and older. The older cohort will form at least 25% of the intended 30,000 trial participants in the US and Mexico. The trial also aims for diversity among the participants, emphasizing the recruitment of racial and ethnic minorities that have been more severely affected by the pandemic, including Black, Latino/x, and Native American communities. The Novavax vaccine is a protein subunit vaccine and requires 2 doses administered 21 days apart.
The Kazakh Research Institute for Biological Safety Problems (RIBSP) also recently initiated Phase 3 clinical trials for its candidate vaccine, an inactivated vaccine that is also delivered in 2 doses administered 21 days apart. The Phase 3 trials will begin with 3,000 participants, but RIBSP is already scaling up production of the vaccine. According to information published by the US National Institutes of Health, the Phase 3 trials are expected to include only 3,000 participants (2,400 in the treatment arm), which is much smaller than the Phase 3 trials for other SARS-CoV-2 vaccine candidates. Additionally, a dedicated production facility is expected to be commissioned in March, which will reportedly be capable of manufacturing 60 million doses per year. Vaccinations could begin as early as March, but like other vaccines, this is contingent on demonstrating safety and efficacy in larger Phase 3 trials and obtaining the necessary regulatory authorization. Additionally, the candidate developed by India’s Zydus Cadila initiated Phase 3 clinical trials, which are expected to include 30,000 participants.
The results of the Phase 3 clinical trials for the Moderna vaccine were recently published in the New England Journal of Medicine. These data have already been published publicly, but they have now completed the peer review process. The Beijing Biological Products Institute has also announced preliminary Phase 3 clinical trial results for the Sinopharm candidate vaccine. According to the press release, the Sinopharm vaccine generated neutralizing antibody response in 99.52% of vaccines and demonstrated 79.34% efficacy. This is slightly lower than the 86% efficacy reported for the vaccine in an earlier trial in the United Arab Emirates, and no additional data were included in the statement.
OTHER VACCINATION NEWS Some early vaccine recipients reported allergic reactions after receiving the vaccine, but these types of reactions are not unique to the new SARS-CoV-2 vaccines. Four (4) vaccine recipients in Germany were reportedly admitted to the hospital after accidentally receiving 5 times the recommended dose for the Pfizer/BioNTech vaccine. The increased dose was accidentally administered to 8 individuals, and 4 were hospitalized for monitoring after experiencing flu-like symptoms. A pharmacist in Milwaukee, Wisconsin (US), was arrested for purposefully storing more than 500 vaccine doses unrefrigerated, which rendered them unusable. In West Virginia (US), 42 prospective vaccine recipients were mistakenly given an injection of the Regeneron antibody treatment instead of the SARS-CoV-2 vaccine. All of the affected individuals are expected to recover with no harmful effects. In New York, a major healthcare network is under investigation after violating the state’s directives by administering vaccinations to members of the general public rather than frontline healthcare workers and long-term care facility (LTCF) residents. The state fined the health system US$1 million for the violation.
NATIONAL SOCIAL DISTANCING & LOCKDOWN As countries around the world begin to implement SARS-CoV-2 vaccination programs or look ahead to future vaccination efforts, some are recognizing the need to strengthen social distancing and other COVID-19 containment measures in response to ongoing surges in transmission. Germany, which leads the EU in terms of vaccine doses administered, is reportedly considering an extension to its national “lockdown,” which is currently scheduled to end January 10. Germany is averaging nearly 18,000 new cases per day, which corresponds to more than 200 daily cases per million population. The UK is entering another period of “lockdown” as well, following the emergence of the B.1.1.7 variant and associated increases in incidence. New national Level 4 lockdowns are now in place in England, Scotland, and Wales, and Northern Ireland increased its national restrictions on December 26. South Africa also strengthened COVID-19 restrictions nationwide to Level 3 on December 29, which orders the closure of beaches and parks in hotspot areas, the closure of bars and pubs nationwide, and prohibits all alcohol sales, among other restrictions.
US ECONOMIC STIMULUS US President Donald Trump signed a US$900 billion COVID-19 economic stimulus package on December 27. He initially rejected the package and insisted that the Congress increase the individual payments from US$600 to US$2,000; however, after the House of Representatives passed a bill to increase the payments, the Senate did not vote on the bill. President Trump subsequently signed the original bill, but the delay caused a disruption in unemployment funding to millions of Americans that rely on this aid following the severe economic consequences of COVID-19.
Under the current bill, Americans enrolled in federal unemployment programs will receive a weekly US$300 unemployment supplement through mid-March. The stimulus package also includes funding for industries that have been severely affected by COVID-19. Additionally, US$82 billion will be allocated for educational resources, including both K-12 and colleges and universities. The package also includes US$285 billion in support for small businesses, including through the Paycheck Protection Program (PPP). Notably, the PPP will have stricter conditions for enrollment than previous stimulus packages, limiting eligibility to businesses with fewer than 300 employees that experienced at least a 25 percent drop in sales. Of that US$285 billion, US$12 billion is specifically set aside for minority-owned businesses. The airline industry will receive US$45 billion to continue to pay employees at a time when the travel and tourism industries continue to experience severe interruptions. Many billions are also set aside to support contact tracing, diagnostic testing, and vaccine distribution efforts.
SARS-CoV-2 VARIANTS Viral mutation is a common, expected process, although genetic changes often do not result in improvements or fitness advantages for the virus. The SARS-CoV-2 variants first identified in the UK and South Africa, however, do appear to have advantageous mutations in the spike protein, which allow the virus to more efficiently enter cells to begin the viral replication process. Emerging evidence indicates that these changes at the cellular and molecular level may result in increased transmissibility for these variants. Furthermore, these variants are emerging as the dominant strains of SARS-CoV-2 in the UK and South Africa, respectively. In response to news of the emerging variants, many countries have implemented travel restrictions for the UK, but the variant has already been identified in at least 37 countries, including the US.
Increased transmissibility of the SARS-CoV-2 variants poses serious problems to pandemic control efforts, especially among already burdened healthcare facilities. Preliminary studies indicate that the SARS-CoV-2 variants do not cause increased disease severity or case fatality; however, an increase in case loads substantially, further straining hospital systems. Social distancing measures—including mask use, physical distancing, and enhanced hygiene practices—will be critical to limit the spread of these new variants. Some scientists and health authorities have expressed concern over the possibility that existing vaccines and vaccine candidates may be less effective against the new variants, but preliminary studies have not found any indication current vaccines will be less effective in protecting against the UK variant. There are fewer studies on effectiveness against the South Africa variant, but research is ongoing. Notably, if current vaccines are determined to be less effective, BioNTech scientists have stated that they could make necessary changes in approximately 6 weeks.
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