EPI UPDATE The WHO COVID-19 Dashboard reports 58.90 million cases and 1.39 million deaths as of 12pm EST on November 24. The WHO reported a new global record for weekly incidence with 4.06 million new cases, a slight increase over the previous week. The WHO also reported 67,225 deaths, an 11% increase over the previous week and another new record high. Additionally, the WHO reported the second highest single-day mortality to date, with 11,863 deaths on November 21.
UNITED STATES
The US CDC reported 12.18 million total cases and 255,958 deaths. The US surpassed 12 million cumulative cases on November 21. From the first case reported in the US on January 22, it took 96 days to reach 1 million cases. From there:
1 to 2 million- 44 days
2 to 3 million- 27 days
3 to 4 million- 15 days
4 to 5 million- 17 days
5 to 6 million- 22 days
6 to 7 million- 25 days
7 to 8 million- 21 days
8 to 9 million- 14 days
9 to 10 million- 10 days
10 to 11 million- 7 days
11 to 12 million- 5 days
The US reported its 3 highest single-day totals on November 19-21, including a record high of 192,673 new cases on November 20. Additionally, the US is currently averaging more than 170,000 new cases per day, which corresponds to nearly 1.2 million cases each week. The US also reported more than 2,000 deaths on November 19 for the first time since May 14*—and the highest daily total since May 7.* The average daily COVID-19 mortality is now 1,498 deaths per day, the highest since May 14, and it appears to be increasing exponentially.
The COVID Exit Strategy website now classifies every state except Hawai’i—including Washington, DC—as having Uncontrolled Spread. Testing volume continues to increase in the US, but it is not keeping pace with increasing transmission in the vast majority of states. In total, only 5 states—plus Washington, DC—are reporting test positivity of 5% or less: Hawai’i, Maine, Massachusetts, New York, and Vermont. In contrast, 14 states are reporting 15% or more. Among the most concerning states are Idaho (40.1%), Iowa (43.1%), Kansas (38.2%), South Dakota (44.1%), and Wyoming (68.7%). The Johns Hopkins Coronavirus Resource Center testing tracker reports 9 states with test positivity of 30% or higher, including Mississippi at 86.0% and Wyoming at 77.2%. Additionally, both the COVID Exit Strategy and Johns Hopkins Coronavirus Resource Center indicate that the majority of US states are reporting increasing test positivity, another concerning sign as the US approaches the holiday season.
There is some evidence that states affected early in the ongoing surge are starting to peak in terms of daily incidence. The vast majority of states continue to report increasing trends, but Iowa (-12% over the past 2 weeks), North Dakota (-7%), and South Dakota (-11%) have all reported decreasing daily incidence over the past week or so. The daily incidence in all 3 states remains elevated, but there is an initial indication that they may have passed a peak. The official CDC data illustrate this well. Additionally, Hawai’i continues to demonstrate the ability to contain its COVID-19 epidemic, reporting a 7% decrease in daily incidence over the past 2 weeks.
Conversely, the COVID-19 epidemics in a number of states continue to accelerate rapidly. Notably, the daily incidence has doubled or more over the past 2 weeks in Louisiana (+190%), New Hampshire (+105%), New Mexico (+125%), and Vermont (+214%). Another 19 states have reported increases of more than 50% over the past 2 weeks. Iowa and North and South Dakota were among the states affected earliest in the current surge, so it would not be surprising if these states peaked earlier than others. With that in mind, reporting is likely to be delayed and erratic, to some degree, over the Thanksgiving holiday weekend, and increased travel as students return home from colleges and universities and individuals and families travel for Thanksgiving will likely factor into transmission and testing volume. It might be a little difficult to monitor epidemiological trends over the coming weeks.
ASTRAZENECA VACCINE AstraZeneca issued a press release regarding preliminary results from the Phase 3 clinical trials of its candidate SARS-CoV-2 vaccine, developed in collaboration with Oxford University (UK). The press release indicates that the vaccine demonstrated 90% efficacy when administered as an initial half-dose followed by a full dose a month later. Interestingly, however, the vaccine was 62% efficacious in participants who received 2 full doses over the same period of time, resulting in an overall efficacy of 70%. No serious adverse events were identified in the trials. In total, the Phase 3 portion of the trials included more than 11,000 participants, and the researchers identified 131 COVID-19 cases. As has been the case throughout the pandemic, the data published via press release have not yet been peer reviewed, although the researchers reportedly intend to publish the full data in the near future.
The increased efficacy among participants who received the initial half-dose has sparked interest among experts. This analysis was based on only 2,741 participants who appear to have received the smaller dose unintentionally, according to a statement by AstraZeneca. The mechanism by which the smaller first dose resulted in higher efficacy is unclear, but representatives from AstraZeneca indicate that this dosing regimen will be investigated further to better characterize its effects. One theory is that the smaller initial dose is not enough to stimulate a full immune response, which could reduce the likelihood that the immune system would suppress the second “booster” dose. At 70% efficacy, the AstraZeneca vaccine could face challenges in terms of regulatory approval, as there are already 2 vaccines with reported efficacy in excess of 90%; however, if the half-dose regimen is, in fact, more efficacious, it could provide a third option.
VACCINE EUA REVIEW The US FDA announced that its Vaccines and Related Biological Products Advisory Committee will convene on December 10 to review the Emergency Use Authorization (EUA) requests submitted by Pfizer and BioNTech for their candidate SARS-CoV-2 vaccine. FDA Commissioner Dr. Stephen Hahn emphasized that while the advisory board “will review the request as expeditiously as possible,” it is unclear how long the review process will take. That being said, this represents another major step toward authorization for a SARS-CoV-2 vaccine. The FDA intends to livestream the meeting via its YouTube, Facebook, and Twitter accounts as well as from the FDA website.
In last week’s press release announcing that Pfizer and BioNTech submitted the EUA request, the companies commented that they would be ready to begin distributing the first doses of the vaccine “within hours after authorization.” Dr. Moncef Slaoui, Operation Warp Speed’s chief scientific advisor, reportedly expects the FDA to grant the first vaccine EUA in mid-December, and in an interview with Wired, US NIH Director Dr. Francis Collins said that he expects the US to be able to fully vaccinate (ie, both doses) 20 million people by the end of December.
RUSSIA VACCINE Russia announced another round of preliminary results from clinical trials of its Sputnik V SARS-CoV-2 vaccine. The interim analysis indicates that the vaccine is 91.4% efficacious at 28 days after the first dose and 95% efficacious after 42 days. The analysis includes data from nearly 19,000 participants, and the researchers identified 39 COVID-19 cases. Efficacy at this level would put the Russian vaccine on par with the 3 other vaccines with recently reported Phase 3 clinical trial data. No serious adverse events were reported. Like other recently reported vaccine trial data, these results have not yet been peer reviewed, but researchers from Russia’s Gamaleya Center intend to publish their analysis in a peer-reviewed journal. In total, 40,000 individuals are participating in the ongoing Phase 3 clinical trials. Coinciding with the announcement, Russian President Vladimir Putin announced at the G20 Summit that Russia is ready to make the vaccine available to other countries. In addition to Sputnik V, Russia is currently developing and testing at least 2 other vaccines.
MONOCLONAL ANTIBODY TREATMENT EUA The US FDA issued an Emergency Use Authorization (EUA) for another monoclonal antibody treatment for COVID-19. The newest EUA is for a combination therapy using casirivimab and imdevimab, developed by Regeneron Pharmaceuticals, which are monoclonal antibodies that target the receptor binding domain for the SARS-CoV-2 spike protein. Similar to the previous FDA EUA for the Eli Lilly monoclonal antibody treatment, this combination is authorized for use in mild or moderate COVID-19 patients (aged 12 years and older) who are not currently hospitalized but who are at high risk of progressing to severe disease. It is not authorized for patients who are currently hospitalized or receiving supplemental oxygen therapy for COVID-19 or an underlying health condition. The 2 products must be administered together.
Reportedly, US President Donald Trump received the combination therapy when he was diagnosed with COVID-19 in October under a Compassionate Use protocol, as the treatment had no formal authorization from the FDA at that time. Regeneron indicated that it expects to have enough supply to treat 80,000 patients by the end of the month; 200,000 by early January 2021; and 300,000 by the end of January. Additionally, Regeneron is partnering with Roche Pharmaceuticals to increase production capacity in early 2021.
MASKS & ASYMPTOMATIC TRANSMISSION In a recent scientific brief, the US CDC examined the community use of cloth masks to mitigate SARS-CoV-2 transmission risk. Cloth masks protect the community both by limiting potentially infectious droplets exhaled by the wearer and by filtering droplets from air inhaled by the wearer. The CDC also stated that mask use is particularly important considering that asymptomatic or presymptomatic individuals are responsible for more than 50% of all transmission.
A recent study conducted in Kansas found that counties that imposed a mask mandate exhibited a decrease in transmission, while counties that did not experienced an increase. The counties with mask mandates reported a 6% decrease in daily incidence, while without a mandate reported a 100% increase over the same period. The study findings are consistent with similar studies conducted in other states that did and did not have mask mandates.
AIR TRAVEL The US is staring down its busiest air travel period since March, in preparation for the annual US Thanksgiving holiday, with volume exceeding 1 million passengers on November 20 and 22. While the US CDC continues to strongly recommend that individuals refrain travel and large gatherings, it has updated guidance to recommend that prospective international travelers get tested before leaving and after returning. Additionally, the CDC recommends quarantining for at least 7 days after travel, regardless of the test results—and 14 days for those who do not get tested after returning. Furthermore, the guidance recommends that individuals delay or cancel travel plans if they test positive or do not receive the results of their testing prior to travel.
Considering the largely rural population of many states currently experiencing COVID-19 surges, small community hospitals can become overwhelmed more quickly than their urban counterparts. Many rural hospitals in Kansas and Missouri have been sending their most critically ill patients to urban, flagship hospitals for care; however, this constant stream of critically ill patients is reportedly starting to overwhelm these larger, better-equipped facilities as well. According to one hospital in Kansas City, Missouri, nearly 25% of COVID-19 patients came from outside of the city. While ventilators and other intensive care equipment must be carefully maintained, many rural providers also report that they are again running low on critical PPE. Some hospitals are rationing gowns, gloves, and N95 respirators in order to extend existing inventory and supply. With these resource constraints, some hospitals are investing in expensive UV-light disinfecting equipment in order to reuse N95 respirators. But with cases still continuing to rise across the US ahead of the holiday season, it is unclear how long hospitals can withstand the added strain before moving to a crisis-standards-of-care approach.
GAZA STRIP Crowding in Gaza, Palestine, is contributing to a dramatic rise in COVID-19 incidence that officials warn could lead to the collapse of the healthcare system, potentially within days. This strain is further complicated by low existing supplies of testing kits, PPE, ventilators, hygiene supplies, drugs, and oxygen-generating machines. Multiple news media reports indicate that the long-standing blockade by Israel and Egypt may also be contributing to supply limitations. One report by Al Jazeera indicates that many in the public have resisted recommendations to wear masks and practice appropriate social and physical distancing, and many continue to participate in large gatherings, which likely contributes to increased transmission. Some senior health officials have advocated for a 2-week lockdown to bring transmission under control, but no new measures have been announced.
CLINICAL COURSE Researchers from US CDC published an article in JAMA that proposes a framework and timeline for the clinical course of disease for COVID-19 patients. The authors break down the disease into 3 phases: [1] an acute phase during the first 2 weeks after symptom onset, characterized by the common acute COVID-19 symptoms (eg, fever, respiratory symptoms); [2] a less-common post-acute hyperinflammatory illness, such as the multi-system inflammatory syndrome in children and adults (MIS-C and MIS-A) that can occur between weeks 2 and 4 after symptom onset; and [3] a later phase of longer-term sequelae, commonly referred to as “long hauler” symptoms, which can occur 1 month or later after symptom onset. The authors explicitly note that patients may not experience all phases, and it is not necessary to experience earlier phases in order to progress to later phases.
STAT News reported that the survival rate among hospitalized patients has increased over the course of the pandemic, due to better clinical management by healthcare providers who have gained a greater understanding of the disease. Additionally, treatment options, including newly authorized drugs (eg, under EUAs), provide a wider range of therapies beyond supplemental oxygen and supportive care. In spite of this progress, increasing transmission, particularly leading into the winter season and holidays, could lead to hospitals being overwhelmed with a wave of new patients requiring hospitalization, which could limit the care available to COVID-19 patients and negatively impact patient treatment and survival.
US CDC COVID-19 TRAVEL ADVISORIES The US CDC published a major update to its COVID-19 travel guidance, including adding a new Alert Level. Previously, CDC travel advisories went through Level 3 (Avoid Nonessential Travel), but in the most recent update, the CDC added a Level 4 travel advisory to its COVID-19-specific travel guidance. Level 4 corresponds to “Very high level of COVID-19,” defined as more than 100 per 100,000 population over the past 28 days for countries with populations greater than 200,000 and more than 100 total cases over the past 28 days for smaller countries. The CDC will also consider secondary data, including hospitalization rates, test positivity, and the rate of change in COVID-19 incidence. The CDC recommends “avoid[ing] all travel” to countries in the Level 4 tier. The CDC moved 179 countries and territories to Level 4, and there remain 59 total countries in Levels 1 (take COVID-19 precautions) and 2 (avoid all nonessential travel), although there are currently no countries in Level 3 (also avoid nonessential travel). The CDC also recommends avoiding travel to 9 territories due to a lack of COVID-19 reporting and unknown COVID-19 status. Notably, the new Level 4 appears to only apply to COVID-19, as the rest of the CDC’s travel guidance only lists 3 levels.
The US Department of State travel advisories utilize a Level 4 (Do Not Travel), which has caused some confusion during the COVID-19 pandemic. Notably, the State Department issued a global Level 4 travel advisory from March to August due to pandemic, and it has issued COVID-19-related Level 4 advisories for many individual countries since then. Prior to the CDC update, the CDC did not utilize an “avoid all travel” travel advisory, so there were discrepancies between the two sets of travel guidance—ie, avoid nonessential travel under the CDC travel guidance vs do not travel under the State Department travel guidance. Now, the situation has reversed, with the CDC recommending that individuals “avoid all travel” to nearly 200 countries and territories, while the State Department has COVID-19-related Level 4 travel advisories for only 25 countries.
CRISIS STANDARDS OF CARE The Johns Hopkins Center for Health Security published a report on lessons from New York City hospitals’ use of crisis standards of care (CSC) during the unprecedented surge of COVID-19 patients in April-June. Many hospitals were overwhelmed and found it necessary to adjust the way in which care was provided in order to focus on providing the greatest overall benefit for COVID-19 patients. The researchers convened a working group consisting of 15 NYC hospital intensive care unit (ICU) directors to discuss challenges and lessons regarding CSC to support hospital systems nationwide as they adapt to the ongoing COVID-19 epidemic.
The working group identified a number of key takeaways and areas for further investigation. Notably, pre-pandemic planning for CSC did not necessarily apply well to COVID-19 environment, and existing plans needed to be adapted in the midst of the surge to account for COVID-19-specific operational realities and clinical needs. The working group members also discussed the importance of inter-hospital collaboration in order to maintain flexible capacity and adapt to dynamic patient surge conditions, and they noted that many clinicians struggled to maintain situational awareness, especially regarding patient load and resource availability. Real-time decision-making regarding patient triage or allocation of limited healthcare personnel or other resources was a major challenge, and healthcare workers experienced mental health and psychological effects due to implementing CSC. Additional research is needed to better operationalize CSC decision-making policies, and CSC plans need to include specific triggers and formal declarations that address the scope of the CSC, including the specific processes and resources to which they apply. Additionally, rapid decision-making processes need to be established to reduce delays in allocating personnel and resources that could endanger patients’ health. One of the biggest limitations during the COVID-19 surge was not equipment, but rather, personnel, which will likely remain a major limitation throughout the US COVID-19 epidemic.
SANTA CLAUS & MENSCH ON A BENCH As the US CDC and other health experts continue to emphasize the importance of social and physical distancing to mitigate SARS-CoV-2 transmission risk, children around the world can rest easy over the upcoming holiday season. Dr. Anthony Fauci recently confirmed that Santa Claus is immune to SARS-CoV-2 infection, due the strength of his “innate immunity.” Santa may not be making his usual holiday appearances in many stores and shopping malls this year, to reduce the risk of children and families spreading the infection in holiday shopping crowds, but he is keeping his traditional schedule to deliver presents around the world on Christmas Eve. Dr. Fauci noted that St. Nick will not pose any COVID-19 risk as he makes his annual journey. Similarly, Neal Hoffman confirmed that Moshe, the Mensch on a Bench, is also immune. Mr. Hoffman created Mensch on a Bench for his son in 2011 as the Jewish counterpart to Elf on a Shelf. Moshe and Kris Kringle are encouraging individuals and families around the world to take the appropriate precautions to protect against COVID-19 over the holidays.
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