EPI UPDATE The WHO COVID-19 Dashboard reports 89.71 million cases and 1.94 million deaths as of 11:45am EST on January 12. Following 2 weeks of decreased global incidence and mortality, coinciding with holidays around the world, the WHO reported new record high weekly totals for both COVID-19 incidence and mortality. The WHO reported 4.95 million new cases last week, a nearly 20% increase over the previous week. The WHO also reported 85,653 deaths last week, an 11% increase over the previous week.
UNITED STATES
The US CDC reported 22.32 million total cases and 373,167 deaths. On January 8, the US reported 314,093 new cases, becoming the first country to surpass 300,000 new cases in a single day. To our knowledge, the US remains the only country to report more than 100,000 new cases in a single day. The US is now averaging 244,702 new cases per day, the highest daily incidence to date and nearly 1 million new cases every 4 days. The US reported a new record for single-day mortality* as well, with 4,180 deaths reported on January 7. The average daily mortality surpassed 3,000 deaths per day for the first time since the onset of the pandemic. The current average of 3,214 is 12.5% higher than the peak mortality during the United States’ initial surge, corresponding to nearly 10,000 deaths every 3 days.
The US CDC reported 25.48 million vaccine doses distributed and 8.99 million doses administered (35.3%). These include 4.24 million doses distributed for use in long-term care facilities, of which 937,028 (22.1%) have been administered.
Distribution of SARS-CoV-2 vaccines continues to scale up nationwide, but the speed at which states are administering vaccinations varies widely. Among US states, all but 7 (and Washington DC) have received between 6,000 and 8,000 doses per 100,000 population from the federal government, illustrating that allocation has been largely consistent nationwide. Arkansas; Hawai’i; Maine; New Mexico; Vermont; Washington, DC; and West Virginia have received between 8,000 and 9,000 doses per 100,000 population, and Alaska has received 18,092 doses per 100,000 population, more than double the per capita total received by any other state.
While the per capita distribution is relatively consistent between states, vaccine administration is a much different story. Most US states have administered between 2,000 and 4,000 doses per 100,000 population. Among those states reporting higher vaccination coverage, Alaska (4,788); Maine (4,088); Vermont (4,128); Washington, DC (4,141); and West Virginia (5,376) are among those that have administered the most vaccine doses per capita. Connecticut is reporting 4,128 vaccines per 100,000 population, and North and South Dakota are reporting 5,100 and 5,451, respectively. On the other end of the spectrum, 9 states are reporting fewer than 2,000 vaccinations per 100,000 population, including Arkansas (1,355) and Georgia (1,346) with fewer than 1,500. Alabama (23.4%) and Arizona (24.5%) are also reporting fewer than 25% of doses administered. 10 states have administered more than half of their received doses. North and South Dakota are the top 2 states, with 72.6% and 70.0%, respectively.
US VACCINATION
FEDERAL DISTRIBUTION
As vaccination efforts continue in the US, operational and policy challenges continue to emerge, some of which are slowing progress. One of the biggest issues with the US vaccination effort is the national distribution system. Under the current plan, the federal government is reserving approximately half of the available vaccine doses in order to ensure that enough supply is available to provide second doses to all vaccinees. In order to speed the United States’ COVID-19 vaccination progress, US President-Elect Joe Biden announced that he intends to release essentially all of the remaining federal inventory soon after taking office. The stated goal of administering 100 million vaccinations in the first 100 days of his term would be a tremendous achievement, particularly considering the US has administered fewer than 10 million doses in slightly less than a month. Efforts are ongoing to establish plans to provide states with additional information regarding future shipments that will enable vaccinators to improve scheduling and administration, but many challenges remain. Even if the federal government increases the distribution to states, there are still many barriers to increasing the pace of vaccination at the local level. Notably, the Biden Administration plan will not delay the second dose, like in some other countries. T he aim is to increase the speed at which the first doses are administered and to provide increased transparency regarding the timing of future shipments to improve planning at the local level. Following the Biden Administration announcement, the US Department of Health and Human Services is expected to announce that the federal government will begin distributing the reserved vaccine doses prior to President-Elect Biden taking office.
SYRINGE VOLUME
As we covered previously, the European Medicines Agency (EMA) updated its guidance for the Pfizer/BioNTech vaccine to recommend the use of “low dead-volume” syringes in order to enable vaccinators to draw an extra, sixth dose from vaccine vials. Reports emerged early in the US vaccination effort that some Pfizer/BioNTech vials contained enough vaccine for a sixth (or sometimes seventh) dose; however, a report published by Politico indicates that some of the syringes distributed nationwide by Operation Warp Speed are not the kind that enable vaccinators to draw extra doses. The syringes are distributed along with the vaccine as part of “ancillary supply kits,” and federal officials are reportedly working on a solution to provide syringes with a smaller “dead-volume” that could increase the number of available doses. At 1 extra dose of vaccine per vial, the overall capacity could increase by 20%, which could translate to an extra 5 million doses, based on the current national distribution. A representative from the American Hospital Association indicated that the syringes included with the most recent distributions of the vaccine have a larger “dead-volume,” which is resulting in fewer doses of the vaccine compared to earlier shipments, posing challenges in terms of ensuring enough vaccine is available to provide individuals with the second dose. A representative for the American Pharmacists Association noted that the federal tracking system is based on the number of vials distributed, not the number of doses administered, so hospitals that receive the same number of vials may not have enough vaccine to provide everyone with a second dose, if they are not able to draw extra doses from each vial like they did previously.
MASS VACCINATION EVENTS
As vaccination efforts scale up nationwide, including expanded eligibility, state and local public health and healthcare officials are proceeding with plans to establish mass vaccination capacity. Some of these efforts are leveraging space available at large venues—such as stadiums, convention centers, and fairgrounds—which can provide space for many vaccinators that can process large crowds quickly. For example, Los Angeles, California, is converting Dodger Stadium from a mass testing site to administer vaccinations. California is reportedly also establishing mass vaccination sites at Disneyland Resort (Anaheim), Petco Park (San Diego), and CalExpo fairgrounds (Sacramento). In San Antonio, Texas, health officials began administering vaccinations at the Alamodome, where they expect to be able to vaccinate 30,000 people per week. With its regular season over, and most teams no longer playing, the NFL (football) is encouraging teams to make their stadiums available to serve as vaccination sites. While these large sites provide the space needed to administer vaccinations rapidly, many barriers still remain, including the logistics of transporting and storing vaccines and the need for additional personnel who are trained and qualified to administer vaccinations.
EMERGING VARIANTS Expanded sequencing and screening capacity and capabilities have helped identify several emerging variants of SARS-CoV-2 in the UK (B.1.1.7) and South Africa (B.1.351). More recently, similar variants were detected in Japan and Nigeria. The B.1.1.7 and B.1.351 variants have several mutations in the spike protein, which appear to confer increased transmissibility. The variant detected in Japan was first identified in 4 travelers from Brazil who arrived at Haneda Airport in Tokyo. The variant identified in Nigeria was first detected in the state of Osun, in specimens dating back to at least August 2020, and preliminary analysis indicates that it is “distantly different” from the B.1.1.7 and B.1.135 variants. Health authorities and researchers are investigating the particular characteristics of the new variants, including any potential effects on transmissibility, disease severity, and vaccine susceptibility.
Although the variants do not seem to cause increased morbidity or mortality, WHO Director-General Dr. Tedros Adhanom Ghebreyesus stated that the continued emergence of highly transmissible variants is “highly problematic.” While these variants may each exhibit similar mutations and characteristics, it appears that they have all emerged independently. The wide geographic distribution of emerging variants is concerning for control efforts, because the emergence and evolution of the virus, including the effects on the virus’ characteristics, are unpredictable. Continued and renewed efforts in genomic surveillance are necessary in order to monitor the geographic spread of existing variants and quickly identify the emergence of new ones.
VACCINATING RECOVERED INDIVIDUALS Since the onset of the pandemic, health experts and officials have studied the role of immunity conferred by natural infection. While reports of are relatively rare, the potential for reinfection does exist. In light of this risk, the US CDC emphasizes that individuals who were previously infected and recovered should still get vaccinated due to the “severe health risks” and uncertainty regarding the duration of natural immunity. Additionally, the degree of natural immunity “varies from person to person.” The duration of the immunity conferred by vaccination remains uncertain as well, but research is still ongoing via clinical trials. Depending on the duration of immunity following vaccination, it may be necessary for individuals to receive regular boosters to provide longer-term protection.
SHORTENED QUARANTINE In December 2020, the US CDC updated its COVID-19 quarantine guidance to offer several options that allow individuals to shorten their 14-day quarantine period following a known exposure to SARS-CoV-2. Specifically, individuals who are unable to quarantine for the full 14 days can end their quarantine after 10 days if they exhibit no symptoms or after 7 days if they test negative on Day 5 or later. The CDC’s MMWR published 2 recent studies that provide analysis of the transmission risk associated with shorter quarantine periods.
The first study was conducted by the US CDC COVID-19 Response Team and the COVID-19 Collegiate Athlete Testing Group, in collaboration with researchers from several US universities. The researchers evaluated SARS-CoV-2 testing data for 1,830 US college athletes who were quarantined and tested after exposure to known COVID-19 cases. Among these athletes, 458 (25%) tested positive at some point during their quarantine period, including 137 who never reported COVID-19 symptoms. Among 620 athletes with positive tests*, 303 (48.9%) had positive tests by Day 2 of quarantine and 453 (73.1%) by Day 5. For those who had a negative test on Day 5, the researchers estimate the risk of testing positive after that point to be 26.9%, including 14.2% after Day 7 and 4.7% after Day 10. Notably, however, 26 of the 29 athletes that tested positive on Days 11-14 were not tested at all prior to that point, so it is possible that they would have tested positive on earlier tests, had they been conducted.
*Including additional data from schools that only reported positive tests.
Officials from the Vermont (US) Department of Health issued recommendations for a shorter quarantine period in May 2020, 7 months before the US CDC update. The Vermont policy stated that individuals could conclude their quarantine period if they tested negative on or after Day 7, based on data indicating that approximately 75% of COVID-19 patients developed symptoms within 7 days of exposure. The researchers analyzed test results for 2,200 contacts of known COVID-19 cases who were tested on Days 7-10 after exposure, collected in May-November 2020. In total, 87 (4%) of these individuals tested positive on Days 7-10, including 24 (25%) who were asymptomatic at the time of testing. The researchers also present data on the results for subsequent testing for a subset of these individuals. Among those who initially tested negative, 262 were tested again within 7 days—154 initially tested on Day 7 and 108 initially tested on Days 8-10. None of those individuals tested positive on the second test, providing evidence that there is relatively low risk of becoming infectious after a negative test later in the quarantine period. This study included data from a small proportion of individuals who ended their quarantine early, but it does provide some evidence that the risk of becoming infectious late in the quarantine period is relatively low.
UK TRAVEL SCREENING & TESTING With the emergence of the B.1.1.7 variant of SARS-CoV-2, the UK has strengthened travel restrictions and increased testing volume. Many countries have implemented their own travel restrictions to decrease the number of travelers arriving from the UK, including some in response to the new variant. The UK, already struggling to keep up with increased incidence believed to be linked to the B.1.1.7 variant, has also implemented strict travel guidance to prevent the entry of other variants, including the B.1.351 variant. Anyone entering the UK by plane, boat, or train must now present a negative SARS-CoV-2 test, taken within 72 hours of departure, before they are permitted to enter the country. Travelers also must fill out a passenger locator form prior to their arrival in order to facilitate contact tracing efforts while they are in the UK. Failure to complete the passenger locator form could result in fines up to £500.
TRANSMISSION ON AIRCRAFT A study published in the US CDC’s Emerging Infectious Diseases journal describes in-flight transmission of SARS-CoV-2 among passengers on a flight from Dubai, UAE, to Auckland, New Zealand—with a stop in Kuala Lumpur, Malaysia. Upon arrival in New Zealand, all passengers were subjected to mandatory 14-day quarantine, with testing conducted at approximately Day 3 and Day 12. Testing identified 7 SARS-CoV-2 infections among the passengers, including 5 that tested negative prior to their departure. Genomic analysis of specimens collected from each passenger found that the viral genome in 6 of the 7 passengers was identical, with 1 mutation present in the seventh passenger. Combined with the timeline of symptoms and positive tests, this suggests that the infection was transmitted among the passengers, rather than from multiple sources prior to travel. While testing negative prior to travel will likely decrease the number of imported cases, by denying travel for those who are already infectious, negative tests only indicate the current state of infection and cannot detect individuals who will be infectious after that point. Travel screening can mitigate the risk of importing cases or transmission during travel, but it cannot prevent them.
HIGH-TITER CONVALESCENT PLASMA A study published in The New England Journal of Medicine, conducted on behalf of the Fundación INFANT–COVID-19 Group, evaluated convalescent plasma with a high IgG titer as a COVID-19 treatment. The randomized, double-blind, placebo-controlled trial included 160 patients in Argentina aged 75 years or older or aged 65-74 years with at least 1 pre-existing condition associated with elevated risk of severe COVID-19 disease and death. The convalescent plasma used in the treatment group included “antibody concentrations in the upper 28th percentile,” and the study participants were divided equally between the treatment and placebo groups (80 in each). The treatment group exhibited a 48% relative reduction in risk of severe respiratory disease compared to the placebo group—13 patients (16%) in the treatment group compared to 25 patients (31%) in the placebo group. Additionally, few patients in the treatment group died than in the placebo group, 2 (2%) compared to 4 (5%), but this result was not statistically significant. No adverse events were reported in either group.
LONG-TERM HEALTH EFFECTS Evidence continues to emerge on the many and varied long-term health effects of COVID-19. Research has already established correlation between COVID-19 disease and certain cardiac, respiratory, and neurological conditions, but it is still unclear for how long these “long COVID” symptoms may persist. A study published in The Lancet followed 1,733 recovered COVID-19 patients from Wuhan, China, who were initially recovered between January and May. Among these patients, 76% reported at least one symptom 6 months after their recovery, including muscle weakness or fatigue (63%), difficulty sleeping (26%), and hair loss (22%). Additionally, 23% of the participants reported anxiety or depression, and 27% reported persistent pain or discomfort. The odds of having persistent symptoms was statistically higher among participants with severe disease—i.e., requiring high-flow nasal cannula oxygen, non-invasive ventilation, or invasive mechanical ventilation—compared to patients who did not require any oxygen therapy (OR= 2.42). Data collection on “long COVID” patients must continue for the foreseeable future to track whether or when these symptoms resolve. The persistence of months- or years-long COVID-19 medical sequelae has significant implications for medical care and public health initiatives in the future, potentially long after the end of the pandemic.
DELIRIUM Mechanical ventilation has been previously associated with an increased risk of acute brain dysfunction, and a study published in Lancet: Respiratory Medicine investigated delirium and coma across critically ill COVID-19 patients. The study included 2,088 adult COVID-19 patients across 69 intensive care units (ICUs) across 14 countries. Patients with a history of mental health issues, neurological conditions, drug overdose, brain damage, blindness, and deafness were excluded. Within the cohort, 1,397 of patients were mechanically ventilated during the same day of ICU admission, and an additional 430 patients were mechanically ventilated at some other time during hospitalization. The researchers evaluated risk factors associated with coma or delirium within 21 days of ICU admission. Invasive mechanical ventilation and the use of restraints as well as the prescription of benzodiazepine (sedative), opioids, vasopressors, or antipsychotic medications were significantly associated with increased risk of delirium the following day. Notably, family visitation, whether in-person or virtual, was significantly associated with a lower risk of delirium (OR= 0.73). The researchers recommended that clinicians avoid continuous infusions of benzodiazepine and use alternative options for sedation. Authors also recommended that care providers arrange safe and appropriate family visitation, either in person or virtually.
mRNA VACCINE PLATFORM Following the success of the mRNA platform used in its SARS-CoV-2 vaccine, Moderna announced that it is expanding its mRNA vaccine development efforts. The 3 new programs will leverage the mRNA technology, successfully demonstrated to be effective in combating SARS-CoV-2, for other pathogens. Moderna will be expanding its research portfolio with 3 mRNA vaccine efforts for seasonal influenza, 2 for HIV, and 1 for Nipah virus, and it already has ongoing mRNA vaccine development efforts for a number of other pathogens. Beyond vaccines, Moderna is also expanding its mRNA research for therapeutics.
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