Sunday, January 24, 2021

January 22: Johns Hopkins COVID 19 Report

COVID-19

Updates on the COVID-19 pandemic from the Johns Hopkins Center for Health Security.

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The Johns Hopkins Center for Health Security produces US Travel Industry and Retail Supply Chain Updates. You can access them here.

The Johns Hopkins Center for Health Security produces weekly updates on SARS-CoV-2 vaccine development, policy, and public perception in the US. This is a resource fromCommuniVax, a research coalition convened by the Johns Hopkins Center for Health Security and the Texas State University Department of Anthropology, with support from the Chan Zuckerberg Initiative. You can access them here.

EPI UPDATE The WHO COVID-19 Dashboard reports 96.01 million cases and 2.08 million deaths as of 5am EST on January 22.

In our COVID-19 updates, we typically focus on epidemiological data, daily or cumulative, in countries or areas where the COVID-19 pandemic is more severe. This week, we will take a brief look at countries and territories that have had relative success in containing SARS-CoV-2.

The global average for per capita cumulative incidence is 12,507 cases per million population, and 106 of 190 countries and territories are reporting fewer per capita cases than that. In total, 31 countries and territories are reporting fewer than 500 cumulative cases per million population, and 15 are reporting fewer than 100. Among this short list are some notable examples that have received attention over the course of the pandemic regarding their success in containing transmission. New Zealand (#30; 472.0 cases per million) managed to interrupt domestic transmission, including a period of 100 days without a documented case of local transmission. China is #13 with 68.5 cases per million, despite facing the first major epidemic, which necessitated a full “lockdown” of more than 10 million people and the rapid construction of emergency hospitals in Wuhan to handle the severe patient surge. Taiwan (#9; 36.5) reported some of the earliest imported cases, but its government quickly implemented a response that included social distancing restrictions, testing and contact tracing programs, and quarantine and isolation for exposed and infected individuals in order to bring its epidemic under control. The top 4 countries—Vanuatu (3.3), Lao PDR (5.6), Tanzania (8.5), and Micronesia (8.7)—are all reporting fewer than 10 cumulative cases per million. The majority of countries reporting fewer than 500 cases per million are located in East, Central, and West Africa; Southeast Asia; and the Western Pacific, including a number of small island nations and territories. None are in Europe or North or South America, which have been impacted by the most severe surges or waves since early in the pandemic.

In terms of per capita cumulative mortality, the global average is 268.1 deaths per million population. In total, 110 countries and territories are reporting fewer per capita deaths than the global average. Of those, 45 are reporting fewer than 20 deaths per million population, including 13 countries with fewer than 5. There is considerable overlap between the lists for incidence and mortality. In fact, 38 countries and territories are among the top 50 in both lists. Much like the geographic distribution for cumulative incidence, most of the top countries/territories in terms of mortality are located in Africa, Southeast Asia, and the Western Pacific. Notably, however, there are also several countries from other regions, including Cuba (#39; 16.2) and St. Vincent and the Grenadines (#43; 18.0) in the Caribbean; Tajikistan (#30; 9.4),and Uzbekistan (#44; 18.5) in Central Asia; and Bhutan (#8; 1.3) and Sri Lanka (#35; 12.9) in Southern Asia. Burundi (0.2), Taiwan (0.3), Tanzania (0.4), and Vietnam (0.4) are all reporting fewer than 0.5 deaths per million.

Our World in Data reports that 55.58 million vaccine doses have been administered globally.

UNITED STATES

The US CDC reported 24.32 million total cases and 404,689 deaths. The US surpassed 400,000 cumulative deaths on January 19.

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

On January 19, the US daily incidence fell below 200,000 new cases per day for the first time since January 1. At this pace, the US could surpass 25 million cumulative cases in the next 3-4 days. Following several days of depressed daily mortality over the Martin Luther King, Jr. Day holiday weekend, the US reported 4,383 new deaths yesterday, the highest single-day total to date*.

*With the exception of April 15, when New York City reported more than 3,700 previously unreported probable deaths from the onset of its epidemic.

The US CDC reported 37.96 million vaccine doses distributed and 17.55 million doses administered (46.2%), including 2.09 million administered in long-term care facilities (LTCFs). In total, 15.05 million people have received at least 1 dose of the vaccine, and 2.39 million have received both doses. The breakdown of doses by manufacturer remains relatively even, with slightly more Pfizer/BioNTech doses administered (9.82 million; 56%) than Moderna (7.72 million; 44%).

The Johns Hopkins CSSE dashboard reported 24.69 million US cases and 411,781 deaths as of 1:30pm EST on January 22.

US PRESIDENTIAL TRANSITION Almost immediately upon taking office, US President Joe Biden took action in the United States’ battle against COVID-19. On January 20, shortly after the President Biden's inauguration, the White House published its national COVID-19 response plan, which highlights priorities such as “listen[ing] to science,” increasing access to testing, bolstering the supply of personal protective equipment (PPE), providing support for schools and businesses, protecting high-risk individuals, and vaccination. The announcement was accompanied by a detailed, 200-page document that outlines goals and policies for a wide range of challenges facing the COVID-19 response.

President Biden also issued several executive orders shortly after taking office, which reversed the United States’ withdrawal from the WHO, established a COVID-19 Response Coordinator position in the White House, and mandated mask use by federal employees and in federal buildings. On January 21, his first full day in office, President Biden issued additional executive orders and directives to address specific aspects of the COVID-19 response, including to bolster the supply chain for critical supplies and equipment (eg, PPE, therapeutics, test kits, vaccines), including through the Defense Production Act; increase financial and operational support for state governments, including through the National Guard; enhance public health data collection and sharing; improve clinical care and expand access to novel therapeutics for COVID-19 patients; implement COVID-19 risk mitigation measures for domestic and international travel; protect worker health and safety; increase testing capacity and build a sustainable public health workforce; support schools and childcare; and promote equity in the COVID-19 response.

The US is also expected to commit funding for the WHO’s COVAX funding program, which will supply vaccines to low- and middle-income countries. President Biden also directed the Department of Education to extend the suspension of federal student loan repayments, reportedly through September 2021. Additionally, senior officials in the Biden Administration are working to develop their SARS-CoV-2 vaccine distribution plan, with the aim of achieving President Biden’s stated goal of 100 million vaccinations in 100 days.

US VACCINATION US States are struggling to maintain sufficient inventory to support their SARS-CoV-2 vaccination efforts, including multiple major cities that anticipate exhausting their supply in the coming days. In a press conference on January 20, New York Governor Andrew Cuomo said the state’s supply of SARS-CoV-2 vaccine for first doses would run out in 2-3 days. In New York City, tens of thousands of scheduled vaccination appointments were cancelled in order to ensure that sufficient reserve is available for second doses. Both New York State and New York City have scaled up vaccination capacity, but they are currently not able to maintain that pace due to supply limitations. There were concerns that San Francisco could exhaust its inventory by Thursday of this week due to limited incoming supply from the federal government and concerns about a lot of Moderna vaccines that caused those doses to be put on hold. California ultimately lifted the hold and released several thousand doses of the Moderna vaccine, which allowed vaccination efforts to continue. Officials in both New York and California have indicated that they are receiving fewer doses than in past weeks, despite expanded capacity and eligibility.

As we covered previously, Governor Cuomo appealed to Pfizer for the opportunity to purchase doses directly from the manufacturer, circumventing the federal government’s distribution system. Since then, several other states have raised the prospect of direct purchases, but the Biden Administration reportedly opposes the idea. A spokesperson for President Biden noted that a centralized national system is needed to “ensure states aren't competing against each other like they did with PPE, ventilators, and tests.” Biden Administration officials have repeatedly emphasized their intent to increase transparency and consistency in vaccine deliveries in order to facilitate longer-term planning at the state level.

EUROPE CONTROL MEASURES Several European countries have enacted new COVID-19 measures, including enhanced “lockdown” restrictions and updated mask guidance, in response to ongoing COVID-19 surges—including new records in some countries—and concerns about the increased transmissibility of emerging variants. One of the biggest efforts across Europe is a shift from cloth masks to medical-grade masks, which offer increased protection against SARS-CoV-2 transmission. Austria and Germany, for example, now require the use of medical-grade masks—including N95 or KN95 respirators or FFP2 surgical masks—on public transportation and some other public spaces (eg, retail stores, restaurants). Reportedly, France is considering a similar measure. In light of increased transmissibility of emerging SARS-CoV-2 variants, these policies hope to mitigate transmission risk through the use of more effective face coverings.

Some European countries are extending their current lockdown measures as well, including Germany (through February 14) and Austria (February 3). The Netherlands is implementing a nationwide curfew, the first of its kind since World War II. The curfew will be in effect from 9pm-4:30am, except for essential activities, and violators could face fines of €95 (US$115). In the UK, Home Secretary Priti Patel announced that fines will be issued starting next week for anyone attending house parties of more than 15 people. Fines will start at £800 (US$1,100) and double for each offence, up to a maximum of £6,400 (US$8,750)*. Existing fines of up to £10,000 for organizers of large gatherings (ie, more than 30 people) will remain in place.

*We have not been able to determine whether the fines will apply just to England or the entire UK.

EMERGING VARIANTS Many questions remain regarding the emergence of new SARS-CoV-2 variants around the world. One of the more prominent questions is whether certain mutations could affect vaccine efficacy. Last week, Dr. Ugur Sahin, co-founder and CEO of BioNTech, stated that he expected the Pfizer/BioNTech vaccine to be protective against the new variants. On January 19, Dr. Sahin and other researchers at BioNTech and Pfizer published (preprint) findings from a study that provides insight into preliminary data on the vaccine’s efficacy against new SARS-CoV-2 variants. The researchers utilized blood sera collected from 16 participants vaccinated in the Phase 1/2 clinical trials to evaluate the neutralizing capacity against the B.1.1.7 variant. The researchers found that the vaccine exhibited “no biologically significant difference in neutralization activity” between the B.1.1.7 variant and the reference strain. Research into the efficacy of existing vaccines against emerging variants continues, which will be critical to understanding the next phase of global vaccination efforts.

New evidence suggests that the B.1.351 variant may be less susceptible to antibody treatments, which also raises concerns about the potential for reduced vaccine efficacy. Researchers in South Africa, where the variant was first identified, published (preprint) findings from a study that evaluated the neutralizing capacity of blood sera collected from 21 COVID-19 patients who recovered after being hospitalized. The B.1.351 (or 501Y.V2) variant appeared to be less susceptible to the antibodies present in the sera specimens, which is cause for concern, considering that the production of such antibodies is the goal of most SARS-CoV-2 vaccines and candidates.

Additionally, analysis from South Africa’s National Health Laboratory Service (NHLS) identified more than 4,000 potential instances of reinfection in South Africa. To date, there have been relatively few documented cases of true reinfection with SARS-CoV-2, but this information raises questions regarding whether the emerging variant could increase that risk. Neutralizing antibodies generated during acute infection tend to provide some degree of protection against future infections, at least for a short period of time; however, if the neutralizing antibodies generate for one variant are less effective against new variants, recovered individuals may be more susceptible to reinfection. Further research is needed to definitively determine whether the 4,000 cases are true reinfections and to characterize any effects from the emerging variant.

The identification of emerging SARS-CoV-2 variants has prompted calls for expanded genomic surveillance globally to monitor for the emergence of novel variants as well as the spread of known variants. Ongoing genomic surveillance programs in South Africa and the UK played key roles in detecting 2 of the most prominent new variants, B.1.1.7 and B.1.351, which are believed to be driving regional surges in transmission. Without these real-time efforts, it is likely that new variants would go unnoticed, at least until their epidemiological effects become evident. Retrospective studies have started examining the timelines associated with the emergence and spread of different SARS-CoV-2 variants, illustrating the importance of active genomic surveillance activities. For example, a study published (preprint) this week by researchers at the University of Arizona (US) suggests that the B.1.1.7 variant was circulating in the US at least as early as November 2020, potentially as a result of multiple independent introductions. Continued sequencing of SARS-CoV-2 specimens in countries around the world is critical to understanding ongoing viral evolution, which can then inform effective public health response, including the development of effective medical countermeasures such as vaccines.

BAMLANIVIMAB Eli Lilly announced that its neutralizing antibody treatment bamlanivimab can reduce the risk of developing COVID-19 disease. In a press release on January 21, the company reported preliminary results from a study conducted among residents and staff at long-term care facilities. The randomized, placebo-controlled study, part of the BLAZE-2 trial effort, involved 965 total participants (299 residents and 666 staff). The researchers found that prophylactic use of bamlanivimab was associated with an 80% decrease in the risk of developing COVID-19 disease after 8 weeks. The full data have not yet been published publicly nor peer reviewed, but the company indicated that it intends to publish the data in the near future.

Eli Lilly’s Chief Scientific Officer, Dr. Daniel Skovronsky, stated that bamlanivimab is not a replacement for vaccines, but rather, it could be an option for emergency prophylaxis following known or suspected exposure. The drug could potentially mitigate the risk of disease when there may not be enough time for a vaccine to stimulate a sufficient immune response. Bamlanivimab previously received an Emergency Use Authorization (EUA) from the US FDA as a treatment for COVID-19, but not as a preventive measure.

ICU SURGE & MORTALITY Researchers in Indiana and California (US) published findings from a study on the association between patient surge in hospital intensive care units (ICUs) and COVID-19 mortality. The study, published in JAMA: Network Open, included data from more than 8,500 patients admitted to 88 Veterans Affairs hospitals across the US (March-August 2020). The researchers found that ICU patients treated during periods of high ICU patient surge were significantly more likely to die, even after discharge. Notably, patients treated in an ICU when demand—defined as the percent of the maximum ICU patient load—was greater than 75% were nearly twice as likely to die compared to patients treated when ICU demand was 25% or less (aHR=1.94).

The statistically significant results held up when stratified by date—March-May 2020 compared June-August 2020, when the patient surge was lower. During the June-August period, no patients were treated in ICUs with more than 75% of the beds filled, but those treated when the facility was at more than 75% of its maximum ICU usage still had nearly twice the risk of death than those treated at ICU demand of 25% or less (aHR=1.90). This illustrates the critical importance of mitigating community transmission and the subsequent impact on hospitals and health systems, even during times of relatively low levels of community transmission and ICU usage.

LONG COVID The UK’s Office of National Statistics (ONS) published data regarding the prevalence of symptoms associated with “long COVID” in patients who recovered from acute SARS-CoV-2 infection. The data indicate that approximately 20% of infected individuals exhibit symptoms for 5 weeks or longer, and 10% report symptoms for 12 weeks or longer. This corresponds to an estimated 186,000 individuals in England with symptoms lasting between 5 and 12 weeks. The findings are based on responses to the UK’s COVID-19 Infection Survey, which utilizes a nationally representative sample from across the UK, and efforts are ongoing to gather additional data, including on symptoms that persist longer than 12 weeks. A more detailed look at the available data shows that prevalence of long COVID symptoms* tends to increase with age, peaking in the 35-49 years (26.8%) and 50-69 years (26.1%) age groups, compared to the 2-11 years (12.9%) and 12-16 years (14.5%) age groups. Additionally, there appears to be a statistically significant increase in prevalence among women (23.6%) compared to men (20.7%).

*Data displayed here refer to the presence of any symptom at 5 weeks, but the provided tables also include data on individual symptoms.

VACCINE CLINICAL TRIALS As more vaccines are authorized for use in countries around the world, it could pose challenges for conducting clinical trials for other vaccines. As we covered previously, there are ethical and practical challenges to keeping clinical trial participants “blinded” to knowing whether they received the candidate vaccine or the placebo, particularly once that particular product is ultimately authorized for use. Another problem is arising in trials for other candidate vaccines, as participants are starting to request that they be “unblinded” in order to determine if they want to get vaccinated with a product that is currently authorized for use. In one example, researchers conducting Phase 3 clinical trials for the Novavax vaccine are reporting that older participants are requesting to be unblinded after some US states expanded eligibility to adults aged 65 and older. Notably, the Novavax trials aim to include adults aged 65 and older as 25% of the study population, which could be a major challenge if adults in this age group are getting vaccinated using the Pfizer/BioNTech or Moderna products, and similar barriers could face any future clinical trials.

There are alternatives to randomized, blinded, placebo-controlled trials—considered to be the gold standard for clinical trials—but these, too, could be challenging for vaccine candidates. One option is a “non-inferiority” trial, which compares a new product to an existing product to determine if the new product performs on par with the existing one. Considering the high efficacy of both the Pfizer/BioNTech and Moderna vaccines, it could be difficult for new products to meet an acceptable threshold. Some of the new candidates, however, do have advantages over existing vaccines that could potentially outweigh shortcomings in terms of efficacy. The Johnson & Johnson (J&J)/Janssen vaccine, for example, would require only 1 dose, which could expand access and speed vaccination programs over 2-dose vaccines. And the Novavax vaccine is expected to be stable at normal refrigeration temperatures (eg, 2-8°C/35.6-46.4°F), as opposed to the freezing or ultra-cold temperatures required for other vaccines, which could make it easier to maintain a cold chain during distribution and longer-term storage, particularly in rural or resource-limited settings.

CHINA QUARANTINE China continues its response to an ongoing COVID-19 outbreak in Shijiazhuang, a city in the northern part of the country. Last week, the Chinese government imposed a “lockdown” on Shijiazhuang and Xingtai. The lockdown then expanded to include other cities across 11 regions in 3 provinces—including Langfang, which is located just south of Beijing. In total, the lockdowns now affect an estimated 22 million people. Additionally, the Chinese government is rapidly constructing a COVID-19 quarantine center outside Shijiazhuang that could house more than 4,000 individuals. The plan is for this facility to host close contacts of confirmed COVID-19 patients as a part of the country’s expansive COVID-19 contact tracing program. The Chinese government has expressed a sense of urgency to control the spread of the pandemic, particularly as the country prepares for increases in travel and large gatherings coinciding with the Lunar New Year in February.

PANDEMIC TREATY At a meeting of the WHO’s Executive Board this week, Director-General Dr. Tedros Adhanom Ghebreyesus expressed support for a recent proposal by the European Council to establish an “international treaty on pandemics.” The proposed treaty could address various aspects of pandemic preparedness, including risk assessment, coordinating research agendas and associated funding, information sharing and event reporting, and improving healthcare access and health system capacity. Notably, international agreements and programs already exist to address preparedness and response for health emergencies like pandemics, including the International Health Regulations (IHRs) and the Global Health Security Agenda (GHSA), and it is not immediately clear what the relationship would be between the proposed pandemic treaty and these existing efforts or how they might complement or overlap with each other. An independent panel of experts recently reported to the WHO Executive Board their findings on the effectiveness of the IHRs, including that the IHRs could be improved upon, but major changes are not necessary.

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