EPI UPDATE The WHO COVID-19 Dashboard reports 86.75 million cases and 1.89 million deaths as of 11:45am EST on January 8.
Brazil, #2 globally in terms of cumulative mortality, surpassed 200,000 deaths, and India, #3 globally in terms of cumulative mortality, surpassed 150,000 deaths. The US remains #1 with 365,000 deaths, and #4 Mexico (131,000) is the only other country with more than 100,000 cumulative deaths.
To date, countries around the world have administered more than 17.5 million doses of SARS-CoV-2 vaccine. The majority of countries that have initiated vaccination efforts are in Europe and North America; however, a number of countries in Asia (China), the Eastern Mediterranean region (Bahrain, Israel, Kuwait, Oman, Saudi Arabia, UAE), and Central and South America (Argentina, Chile, Costa Rica) have begun vaccinating their populations as well. We are not aware of any ongoing vaccination efforts yet in Africa or Oceania.
At this point in time, national vaccination totals are not being updated at regular intervals, with some data dating back to December 28, which makes it difficult to form an accurate picture of the current state of vaccination efforts. Based on the most current data available, the US is #1 in terms of total doses administered (5.92 million), China is #2 (4.5 million; December 31), and Israel is #3 (1.69 million). Israel is also #1 globally in terms of per capita doses administered with 19.55 doses per hundred population, which is more than double the coverage in #2 UAE (9.52), more than 4 times #3 Bahrain (4.25), and more than 10 times the UK (1.91; January 3) and US (1.79).
UNITED STATES
The US CDC reported 21.26 million total cases and 359,849 deaths. We expect the US to surpass a cumulative total of 366,000 deaths in the next several days, which would correspond to 1,000 deaths per day for an entire year (2020 was a leap year). The first US death was not reported until February 29, however, so the actual timeline is closer to 10 months—corresponding to 1,170 deaths per day since the first reported US death.
Yesterday, the US reported 299,904 new cases, a new single-day record. This brings the average daily incidence to 228,003 new cases per day, surpassing the pre-holiday peak and setting a new record—a 27% increase over the holiday low of 179,791. The US also reported a new record high for single-day mortality*, with 3,844 new deaths. The US has reported 2 of the 3 highest daily mortality totals* over the past 2 days. The average daily mortality climbed to 2,664 deaths per day, which returns to the pre-holiday level—an increase of 21% over the holiday low of 2,200. It will potentially several more weeks before we begin to see the effects of holiday travel and gatherings.
The US CDC reported 21.42 million vaccine doses distributed and 5.92 million doses administered (27.6%). These include 3.77 million doses distributed for use in long-term care facilities (LCTFs), of which 603,313 (16.0%) have been administered.
EMERGING VARIANTS Information and analyses continue to emerge about newly identified SARS-CoV-2 variants, most notably B.1.1.7 (first identified in the UK) and B.1.351 (first identified in South Africa). Both variants appear to be more transmissible than the variants that circulated earlier in the pandemic, including those that are still circulating widely in most places around the world, but research is ongoing to fully characterize them. Perhaps the biggest concern is the potential that these variants could be less susceptible to newly authorized vaccines or therapeutic drugs. Preliminary research (preprint), conducted by researchers at Pfizer and the University of Texas Medical Branch (UTMB), provides evidence that the Pfizer vaccine is efficacious against both the B.1.1.7 and B.1.351 variants. The study was conducted on blood specimens collected from vaccinated individuals, as opposed to data collected from clinical trials in humans, but it does provide initial confidence that the vaccine will remain a capable tool against the new variants.
Another study published recently (preprint) by researchers at the Fred Hutchinson Cancer Research Center (Seattle, Washington, US), analyzed the effects of various mutations on the virus’ susceptibility to antibody treatments. The researchers found that variants with the E484K mutation, such as the B.1.351 variant, “have greatly reduced susceptibility to neutralization by the...serum antibodies of some individuals.” In fact, they observed decreased neutralization on the order of 10-fold or greater for variants with this mutation. They believe this is a result of changes to the receptor binding domain, which stimulates the majority of the antibody response. Notably, the researchers found that the N501Y mutation present in the B.1.1.7 variant “is unlikely to greatly affect neutralization by most human sera,” an encouraging indication. Further research is needed to better characterize the effects of these and other emerging variants—including their effects on disease severity, transmissibility, and susceptibility to medical countermeasures —but these studies provide insight into the potential impact these variants can have on the COVID-19 pandemic.
VACCINE AUTHORIZATIONS On January 4, the Israeli Ministry of Health authorized the use of the Moderna vaccine, the first country to do so outside of North America. The Israeli MOH has reportedly secured 6 million doses of the vaccine, and the first deliveries were expected earlier this week. On January 6, the European Medicines Agency (EMA) recommended a conditional marketing authorization for Moderna’s SARS-CoV-2 vaccine. The European Commission issued the conditional authorization, making the Moderna vaccine the second vaccine authorized for use in the EU, after the Pfizer/BioNTech vaccine was authorized in December. The EU has purchased as many as 160 million doses of the Moderna vaccine, which are set to be delivered between now and September, adding to the 300 million doses of the Pfizer/BioNTech vaccine already ordered. Additionally, the EMA recommended an update to the Pfizer/BioNTech vaccine guidance “to clarify that each vial contains 6 doses of the vaccine.” The update recommends using “low dead-volume” syringes, which result in moderate improvements in vaccine wastage that can allow vaccinators to draw a full sixth dose from each vial, instead of 5. The EMA announcement notes that “standard syringes..may not [enable vaccinators] to extract a sixth dose.” Additionally, the European Commission reportedly offered Member States the opportunity to purchase as many as 300 million total additional doses, which could bring the total Pfizer/BioNTech allotment to 600 million across Europe. The combined 760 million doses could provide full vaccination for 380 million people, covering approximately 80% of Europe’s population.
VACCINE CLINICAL TRIALS According to multiple news media reports, Brazilian health officials announced that China’s Sinovac SARS-CoV-2 vaccine demonstrated 78% efficacy in Phase 3 clinical trials. With its COVID-19 epidemic largely contained, China coordinated with countries with more widespread transmission to conduct clinical trials. According to the US NIH clinical trial database, the Phase 3 trials in Brazil included 13,000 total participants, less than half the size of the study populations for the Pfizer/BioNTech and Moderna Phase 3 trials. Following these results, vaccine supplies have shipped around the world, waiting for its anticipated approval. Sinovac has already pledged 300 million doses to low- and middle-income countries, approximately half of the expected production capacity for 2020. Previously, researchers in Turkey announced that the Sinovac vaccine resulted in 91% efficacy in a clinical trial of 7,300 participants. To our knowledge, final Phase 3 data and analysis for the Sinovac vaccine has not yet been published publicly.
LOS ANGELES The burden of COVID-19 patient surge on hospitals and health systems can take many forms. While much of the coverage of these issues focuses on hospital beds, personnel, personal protective equipment, and ventilators, general medical supplies are also a major concern. In particular, oxygen supply is emerging as a constraint. Health experts previously forecast oxygen supply as a major concern in some parts of the world, and these concerns are now coming to fruition.
Additionally, EMS personnel in LA are directed to not transport cardiac arrest patients to hospitals if efforts to revive breathing or pulse in the field are not successful. Patients who can be resuscitated on site will still be transported to the hospital for treatment as usual. As we have covered previously, Los Angeles County hospitals are facing a major surge in COVID-19 patients, which has resulted in long lines for ambulances to drop off patients at the hospital, some lasting several hours, which is negatively impacting care for both COVID-19 and non-COVID-19 patients. The new policy aims to reduce the wait time for ambulances to drop off patients by not transporting patients who are unlikely to survive.
CLINICAL TRIAL PLACEBO GROUP VACCINATIONS One of the principal ethical challenges stemming from SARS-CoV-2 vaccine clinical trials is how to handle participants in the control group after vaccines are authorized for use. As a necessary part of randomized controlled trials, some participants receive the vaccine, and others receive a placebo. But now that authorized vaccines are available, it raises questions regarding when those who received the placebo can be eligible to receive the actual vaccination. The longer the control group goes unvaccinated, the more data researchers can collect to evaluate the vaccine’s safety and efficacy, particularly for determining its effect on mitigating infection and transmission risk; however, delaying vaccination for individuals who voluntarily placed themselves at risk to participate in the trial raises ethical concerns.
Negotiations between Pfizer, Moderna, and the US FDA have attempted to address this issue and balance the value of continued data collection against fairness to the trial participants. A recent agreement between Pfizer and the FDA will allow trial participants in the control group to be vaccinated by March 1, if they choose to do so, several months earlier than the original timeline. Moderna established a similar plan in December. Under the new plan, study participants can request to find out whether they received the vaccine or the placebo, and those who received the placebo will be immediately eligible to receive vaccine, even if they would not be eligible under the existing federal guidance.
DIABETES RISK A study published in The Lancet: Diabetes & Endocrinology evaluated the risk of COVID-19 disease and death among patients with diabetes. The researchers collected data on the entire population of Scotland, and focused on the country’s “first wave” of COVID-19 (March-July 2020). The researchers compared the cumulative COVID-19 mortality and the incidence of COVID-19 cases that required critical care among individuals with and without diabetes. The combined odds of requiring critical care or dying from COVID-19 (in or outside of a hospital) was significantly higher among individuals with diabetes (aOR=1.4). The odds of requiring critical care or dying was even higher for patients with Type 1 diabetes (aOR=2.4). Diabetes has been previously identified as a preexisting condition associated with elevated risk of severe COVID-19 disease and death, and this study provides further quantitative data to support that association.
The US CDC lists type 2 diabetes as a condition associated with increased risk and type 1 diabetes as a condition that “might be” associated with increased risk. Notably, this study identified higher risk of severe disease and death among individuals with type 1 diabetes than those with type 2 diabetes, but both were significantly associated with increased risk. Further study is needed to more fully characterize the effects of both types of diabetes on COVID-19 disease.
WHO INVESTIGATION The WHO has deployed a team to China to investigate the origin of the SARS-CoV-2 virus, but the team members are reportedly facing challenges entering the country. According to multiple news media reports, the Chinese government denied entry to the team because their visas had not yet been approved. Several team members had already started their travel when the WHO was notified of the delay in processing the visas, others had to delay their travel, and at least one team member was forced to return home. At his first press conference of 2021, WHO Director-General Dr. Tedros Adhanom Ghebreyesus expressed disappointment that China had not yet finalized the visas. He emphasized the importance of the mission and noted that he had been assured that Chinese officials were working to quickly resolve the issue. A spokesperson from China’s Ministry of Foreign Affairs reportedly indicated that the delay was the result of a “misunderstanding” and that Chinese officials were coordinating closely with the WHO to resolve the issue. The WHO investigation aims to determine the evolution of the SARS-CoV-2 virus, identify animal hosts, and understand the process and timeline by which the virus made the jump from animals to humans.
US VACCINATION Earlier this week, Nebraska (US) Governor Pete Ricketts stated that undocumented workers in meatpacking facilities would not be eligible to receive COVID-19 vaccines. The governor’s communication director reportedly attempted to clarify Governor Ricketts’ comments, indicating that citizens and legal residents would be prioritized over undocumented immigrants. A number of health and immigration policy experts and elected officials expressed opposition to Governor Ricketts’ policy, noting that many meatpacking facilities do employ undocumented immigrants, and that employees at these facilities are at risk for COVID-19, regardless of their immigration status.
Nebraska’s meatpacking industry is among the largest in the US, and 66% of its meatpacking workers are immigrants. According to data published by the Migrant Policy Institute, at least 14% of meatpacking workers are undocumented. In total, more than 52,000 COVID-19 cases nationwide have been reported among meatpacking workers, including 266 deaths. The Midwest Center for Investigative Reporting found that Nebraska reported the highest number of COVID-19 cases originating from meatpacking facilities of all US states, illustrating the risk to these workers. To date, 23 Nebraska meatpacking facilities have reported COVID-19 outbreaks, resulting in 5,267 cases and 22 deaths among meatpacking workers.
INDONESIAN VACCINATION The Indonesian Ulema Council, “Indonesia’s highest Islamic body,” announced that it determined China’s Sinovac SARS-CoV-2 vaccine to be halal, or “fit for consumption by Muslims.” The decision was made based on the Council’s deliberations on potential religious barriers to using the vaccine, including the inclusion of pork-derived gelatin commonly used as a stabilizer in vaccines. Similar concerns exist for members of the Jewish faith as well. Spokespersons for the manufacturers of multiple leading vaccines—including Pfizer, Moderna, and AstraZeneca—have indicated that no pork products are included in their SARS-CoV-2 vaccines.
Notably, the approval by one body is not necessarily universally accepted, but the Indonesian Ulema Council decision is a promising step in the complex effort to mitigate hesitancy surrounding the new SARS-CoV-2 vaccines. Conversations around the religious standing of vaccine candidates have created barriers in past vaccination campaigns, and it is important that these concerns are addressed fully when planning vaccination efforts. Reportedly, the vaccine is still being evaluated for authorization by Indonesia’s national regulatory authorities, which is required before vaccination efforts can begin.
ALLERGIC REACTIONS A study published in the US CDC’s MMWR provides detailed data on allergic reactions following receipt of the first dose of Pfizer/BioNTech SARS-CoV-2 vaccine. The Vaccine Adverse Event Reporting System (VAERS) reported 21 cases of anaphylaxis among a total of 1,893,360 first doses of the vaccine administered between December 14-23, 2020. The 21 cases represent a rate of 11.1 cases per million doses administered. Among the 21 reported anaphylactic reactions, 17 affected individuals had a documented history of allergies or allergic reactions, and 7 had a history of anaphylaxis. Of the cases, 71% occurred within 15 minutes of vaccination, and 18 were reported within 30 minutes. No deaths were reported among anaphylaxis patients. Since the study period, an additional 8 cases have been reported for a total of 29 cases of allergic reactions nationwide. In addition to anaphylaxis, 83 cases of nonanaphylaxis allergic reactions were reported in VAERS (87% documented as nonserious).
INDIA VACCINE The Serum Institute of India announced that it will first focus on supplying India with the Oxford University-AstraZeneca COVID-19 vaccine, approved January 3 for emergency use, before distributing to other countries. The Serum Institute is the world’s largest vaccine manufacturer by volume, and it has been contracted to produce 1 billion doses of SARS-CoV-2 vaccine. Serum Institute CEO Adar Poonawalla indicated that the first 100 million doses are being sold to the Indian government at a special price of 200 rupees (US$2.74) per dose, while the price for the private market will be 1,000 rupees (US$13.68). There is an existing contract with COVAX for 100 million doses each of the AstraZeneca-Oxford and Novavax vaccines, and Mr. Poonawalla says contract negotiations are ongoing to add another 300-400 million doses to that order; however, the export of vaccines for COVAX is not expected to begin until March or April 2021. He also indicated that the company plans to provide 200-300 million doses of the vaccine to COVAX by December 2021. The Financial Times reports that the Serum Institute expects to sell 2-3 million doses to private facilities for US$8 per dose after fulfilling its contract with the Indian government, but this has raised some concerns that the private sale of vaccine doses could shift access from those in the most need to those who can afford to purchase it.
IMMUNITY DURATION Researchers in California and New York (US) published findings from a study on the duration of immune memory response following SARS-CoV-2 infection. The study, published in Science, looked specifically at the role of B cells and CD4+ and CD8+ T cells, as opposed to the neutralizing antibodies analyzed in many other studies. While neutralizing antibodies are the key to preventing infection, immune memory, including B cells and T cells, is expected to play a larger role in preventing or mitigating the severity of disease. The study involved 188 participants who had recovered from SARS-CoV-2 infection—including “a range of asymptomatic, mild, moderate, and severe COVID-19 cases”—recruited in California and New York. Among the participants, 97% were symptomatic during their infection. Blood specimens were collected between 6 and 240 days after symptom onset, including 51 participants who provided multiple specimens over a period of several months.
The researchers observed an increase in the level of B cells corresponding to the SARS-CoV-2 spike protein over the period from 1 month after symptom onset to 6 months or longer. Conversely, the quantity of CD4+ and CD8+ T cells decreased over time, with a half-life of approximately 3-5 months. Additionally, B cells corresponding to the spike protein and the receptor binding domain (RBD) were significantly higher in hospitalized patients than in non-hospitalized patients. Conversely, CD8+ T cells were approximately the same in hospitalized and non-hospitalized patients, and CD4+ T cells were lower in hospitalized patients than in non-hospitalized patients (but not statistically significant). The researchers indicate that the temporal trends in the B and T cells are “consistent with the hypothesis” that the immune memory response is capable of “reduc[ing] COVID-19 disease severity.” While this is a relatively small study, it provides insight into the temporal dynamics of the human immune response to SARS-CoV-2 infection and the potential impact on lasting immunity.
ETHIOPIA A report by the UN Office for the Coordination of Humanitarian Affairs published an update on the humanitarian crisis in Ethiopia’s Tigray Region, describing the humanitarian situation as “dire.” Violence in the region has cut off hundreds of thousands of people from humanitarian aid, including several major cities. The Tigray Region is home to approximately 6 million people, and ongoing conflict has weakened the local health system. The report indicates that only 5 of the region’s 40 hospitals are physically accessible and that the spread of SARS-CoV-2 is a growing concern. Notably, COVID-19 surveillance has been interrupted for at least a month, and the humanitarian response has only been able to implement “limited prevention activities,” including the distribution of PPE and educational materials. The UN report that the displacement of refugees and overcrowded living conditions could be driving “massive community transmission.”
TOKYO Like many countries around the world, Japan is currently facing a major COVID-19 surge, its largest by a factor of 3. In response to increasing transmission in Tokyo, Japanese Prime Minister Yoshihide Suga declared a state of emergency for the city and strengthened COVID-19 restrictions. The state of emergency is currently scheduled to last for a month, through February 7. One of the primary measures is for the public to refrain from nonessential activities, particularly at night, and observe a requested 8pm curfew. The new measures also focus heavily on restaurants and bars, including requested restrictions on the hours they serve alcohol—i.e., not between 7pm and 11am. In order to promote compliance, some of the restrictions are tied to financial support for businesses as compensation for lost revenue, and the government is able to “name and shame” businesses that violate the measures.
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