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EPI UPDATE The WHO COVID-19 Dashboard reports 123.4 million cases and 2.7 million deaths as of 11am EDT on March 23. The global weekly incidence increased for the fourth consecutive week, up to 3.3 million new cases (7.9% more than the previous week). After 6 consecutive weeks of decreases, the global mortality increased last week as well, up to 60,414 global deaths (2.5% more than the previous week). If this is the beginning of a longer-term trend, it would correspond to a 4-week lag behind the global weekly incidence, consistent with the pattern exhibited throughout the pandemic.

Global Vaccination
The WHO reported 398.0 million vaccine doses administered globally, including 226.0 million individuals with at least 1 dose. The dashboard does not yet include data for daily or weekly vaccinations or fully vaccinated individuals.

Our World in Data reports that 458.1 million cumulative vaccine doses have been administered globally, a 19% increase compared to this time last week. The daily average continues to increase, up to 10.6 million doses per day (+6% compared to the previous week). At least 146 countries and territories are reporting national vaccination data.

The US CDC reported 29.7 million cumulative cases and 539,517 deaths. Daily incidence continues to level off at approximately 53-54,000 new cases per day. While this is an 80% decrease from the peak in January 2021, it is only 20% less than the peak during the summer 2020 surge. Daily mortality is beginning to taper off as well. The CDC has reported an average of approximately 1,000-1,050 deaths per day over the past 5 days.

On March 19, the CDC reassigned more than 80,000 previously unreported cases in Missouri (reported on March 8) to the correct dates. The correction caused the average daily incidence for January 11, 2021, to exceed 250,000 new cases per day, making the US the only country to surpass that benchmark to date. The US was also the first, and remains the only, country to surpass 100k, 150k, and 200k new cases per day.

While the national-level trends are leveling off, a number of states are reporting increasing daily incidence*. These states are mostly distributed across the Midwest and Northeast regions, but case counts in Idaho, Maryland, and West Virginia are also increasing. Perhaps the largest resurgence is in Michigan, which has reported increasing trends since February 22. After peaking in early December 2020, Michigan’s daily incidence decreased by 90% before rebounding. Michigan’s daily incidence has nearly tripled since February 22—currently 2,997 new cases per day—and it appears to still be accelerating.
*In an effort to be consistent with respect to the timing of the most recent data, we are using official data reported to the CDC. The data published on the state COVID-19 websites referenced in this section may vary.

New Jersey’s autumn/winter surge peaked in early January and then leveled off briefly from February 19-February 26 before increasing again. Unlike many states, New Jersey’s daily incidence only declined 50%—from approximately 6,000 new cases per day** to 3,000—before rebounding. New Jersey is now reporting 3,980 new cases per day, higher than its first peak in April 2020, and increasing steadily. Maine’s epidemic also rebounded almost immediately after its autumn/winter surge, falling 80% from January 14 to February 22—624 to 131 new cases per day—before increasing immediately back up to 206, a 50% rebound. 
**With the exception of the week following January 7 and 8, when New Jersey reported 23,925 and zero new cases, respectively, which resulted in aberrations in the average values.

The current surge in several states started more recently. After coming down from the peak of its autumn/winter 2020 surge, Maryland’s daily incidence began to increase again relatively quickly. Maryland’s lull lasted from approximately February 20-March 7, and its average daily incidence has increased nearly 25% since then, up to 949 new cases per day. Idaho (312), Massachusetts (1,566), and West Virginia (336) followed similar trajectories, with small bumps following their autumn/winter surges—approximately February 22-March 8***—and then a steady increase in daily incidence of approximately 25% or more. In Minnesota, the daily incidence held relatively steady for most of February at approximately 775-800 new cases per day, but it also started to surge on March 8. Minnesota is currently reporting 1,118 new cases per day, approximately 40% higher than in February. In New Hampshire, the decline in daily incidence leveled off at 200-220 new cases per day from March 5-10 before climbing back up to 275, a 25-35% increase and still rising. Pennsylvania is just beginning to exhibit increasing daily incidence, up from 2,473 new cases per day on March 13 to 2,949 on March 21 (+19%).
***The President’s Day holiday was February 15, so weekly averages in the following week were artificially depressed due to reporting delays and interruptions.

Following the decline in daily incidence in the wake of the autumn/winter 2020 surge and expanding vaccination efforts, many states are relaxing or eliminating COVID-19 restrictions. Most of the country has not yet been vaccinated, however, and there is evidence of increasing prevalence of emerging variants, both of which could increase COVID-19 risk. It will be critical to monitor the epidemiological trends in these and other states over the next several weeks in order to mitigate the risk of another surge.

US Vaccination
The US CDC reported 156.7 million SARS-CoV-2 vaccine doses distributed and 126.5 million doses administered. This includes 82.8 million people (24.9% of the entire US population; 32.0% of the adult population) who have received at least 1 dose of the vaccine and 44.9 million (13.5%; 17.4%) who are fully vaccinated. Among adults aged 65 years and older, 69.2% have received at least 1 dose and 42.5% are fully vaccinated.

The average doses administered* continues to level off at approximately 2.3 million doses per day, including 901,311 individuals fully vaccinated (i.e., second dose of a 2-dose vaccine or a single dose of a 1-dose vaccine). In terms of full vaccination, 22.2 million individuals have received the Pfizer-BioNTech vaccine, 20.3 million have received the Moderna vaccine, and 2.4 million have received the J&J-Janssen vaccine.
*The US CDC does not provide a 7-day average for the most recent 5 days due to anticipated reporting delays for vaccine administration. This estimate is the most current value provided.

The Johns Hopkins Coronavirus Resource Center is reporting 29.9 million cumulative cases and 543,057 deaths as of 11:30am EDT on March 23.

ASTRAZENECA-OXFORD VACCINE PHASE 3 TRIAL AstraZeneca announced preliminary results from a Phase 3 clinical trial for its SARS-CoV-2 vaccine, developed in collaboration with the University of Oxford. The trial included more than 32,000 participants in Chile, Peru, and the US, including 21,583 who received at least one dose of the vaccine. The press release reports an overall efficacy of 79% against any COVID-19 disease among all age groups and 80% efficacy for adults aged 65 years and older. Additionally, the press release describes 100% efficacy against severe disease and hospitalization. AstraZeneca explicitly noted that an independent review of the safety data “found no increased risk of thrombosis or events characterised by thrombosis” associated with the vaccine. Previous analysis of data from trials in Brazil, South Africa, and the UK estimated the overall efficacy to be 60%.

AstraZeneca has not yet published the full clinical trial data—including the number of severe cases and hospitalizations among the placebo group nor data pertaining to emerging variants—and the results have not yet been subjected to peer review. The press release indicates AstraZeneca is continuing to analyze the trial data to prepare a final analysis for submission to the US FDA. The AstraZeneca-Oxford vaccine has received a conditional marketing authorization in the EU and similar emergency use authorizations in a number of other countries as well as an emergency use listing from the WHO, but it has not been granted an Emergency Use Authorization from the US FDA. Similar to the J&J-Janssen vaccine, the AstraZeneca-Oxford vaccine does not require freezer (or ultra-cold freezer) temperatures for storage and transportation, which reduces logistical and operational barriers to mass vaccination efforts.

Today, the US National Institute of Allergy and Infectious Diseases (NIAID) issued a statement that called into question the vaccine’s efficacy estimate. The statement indicated the Data Safety Monitoring Board (DSMB) that oversaw the clinical trials had concerns regarding the efficacy reported in the press release. In particular, the DSMB expressed concern that “outdated information” was included in the calculation, “which may have provided an incomplete view of the efficacy data.” No further details were provided, but the NIAID called on AstraZeneca to work with the DSMB to identify and correct any issues. In response, AstraZeneca stated the preliminary results were based on a “pre-specified interim analysis” of a subset of data collected through February 17. AstraZeneca indicated that it is validating its statistical analysis and engaging with the DSMB, with the goal of publishing the primary results in the next 48 hours. 

ASTRAZENECA-OXFORD VACCINE HESITANCY AstraZeneca’s announcement of results from Phase 3 clinical trials, combined with statements last week from the European Medicines Agency (EMA) and WHO supporting the AstraZeneca-Oxford vaccine’s safety, appeared poised to provide a boost in confidence in the vaccine, but questions regarding the accuracy of the trial’s efficacy analysis threaten to further erode public trust and interest. While the most recent issues may be more of an issue with AstraZeneca’s communications than the vaccine itself, the misstep could taint the public’s impression of the vaccine. In fact, Chief Medical Advisor to the President Dr. Anthony Fauci described the issue as an “unforced error” by AstraZeneca that could have an unfortunate negative effect on the public’s perception of what is “very likely a very good vaccine.”

Recent surveys conducted in several European countries found a substantial portion of the population still believes the vaccine is unsafe. Notably, 61% of French respondents indicated that they felt the vaccine is unsafe, up 18% compared to results from February. Similarly, 55%, 52%, and 43% of German, Spanish, and Italian respondents, respectively, expressed concern about the vaccine’s safety. In Spain and Italy, the new totals are 27 percentage points higher than in February. The UK—where the vaccine was originally developed—was the only country to express confidence in the vaccine, with nearly 75% believing the vaccine is safe.

In addition to challenges of public perception, the AstraZeneca-Oxford vaccine finds itself in the middle of a battle between the EU and the UK regarding access. Reportedly, the European Commission continues to evaluate a “ban” on exporting doses of the vaccine manufactured in the EU in order to direct those doses to meet contractual commitments to EU countries before allowing them to be delivered outside the bloc, including to the UK. Reportedly, the EU has received only one-third of its doses of the AstraZeneca-Oxford vaccine, and the UK has been able to vaccinate approximately 40% of its population, compared to less than 12% across the EU. Officials from AstraZeneca noted that the UK contracts were signed before the EU contracts, which likely factors into the company’s allocations.

PASC/LONG COVID Researchers from the COMEBAC Study Group published data in JAMA from a cohort study describing 4-month outcomes for patients who were hospitalized with COVID-19 in Paris. Among 478 participants contacted by telephone, 244 patients (51%) reported they were experiencing at least 1 new symptom 4 months post-hospitalization. The most common complaints were fatigue (31%), cognitive impairment (21%), and dyspnea (ie, difficulty breathing; 16%). In addition, 63% of 171 patients assessed at follow-up ambulatory visits had abnormal lung CT scans, although the researchers note that lasting severe pulmonary impacts are not uncommon among COVID-19 survivors. The researchers emphasize their data is limited by the lack of a control group and pre-COVID baseline data. 

Another study published in The Annals of Clinical and Translational Neurology by researchers from Northwestern University describes the experiences of patients treated at the university’s specialized clinic for patients experiencing COVID-19-related neurological symptoms. The study included 100 patients from 21 states (50 testing positive for SARS-CoV-2 but non-hospitalized, and 50 testing negative for SARS-CoV-2; average age of 43) who were treated between May and November 2020. The most frequently reported neurologic manifestations included “brain fog” (81%), headache (68%), numbness/tingling (60%), dysgeusia (altered taste; 59%), anosmia (loss of smell; 55%), and myalgias (55%). The researchers note that only anosmia was significantly more frequent in patients who tested positive than those who tested negative (74% vs 36%) and that positive patients performed worse in attention and working memory cognitive tasks when compared to a demographic‐matched US population.

Several experts are calling for media outlets to be cautious in their reporting of so-called “long COVID,” collectively referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC). They note some patients who describe long-lasting symptoms of COVID-19—including gastrointestinal symptoms, “brain fog,” severe fatigue, hair loss, and headaches—never tested positive for SARS-CoV-2. They also emphasize these symptoms are associated with many conditions and are common in the general population, especially among individuals experiencing social and emotional distress. But the experts also call for more study on the potential long-term impacts of SARS-CoV-2 infection, but they caution against “getting ahead of the evidence.” As we reported previously, the US National Institutes of Health in February launched a US$1.15 million initiative to study the potential long-term health impacts of COVID-19. 

SPRING BREAK US colleges and university students typically visit popular warm-weather destinations for spring break for a vacation from classes. This year, the combination of the timing of spring break, unusually discounted prices on accommodations and travel, and efforts to ease COVID-19 restrictions in Florida have made officials concerned that mass gatherings could lead to local and national spikes in transmission. On Saturday, tens of thousands of spring breakers converged on Miami Beach, leading city officials to declare a state of emergency for 3 days, including a curfew imposed from 8pm-6am for all non-essential travel and operations. Traffic also was shut down in certain areas, and indoor and outdoor dining establishments in high-traffic areas were ordered to cease operations starting at 7pm through the duration of curfew.

Local law enforcement have made more than 160 arrests in the past week related to gatherings—often citing lack of proper mask use, overcrowding, violence, or damage to local property. Law enforcement officials fired pepper spray-filled balls to break up crowds, among other measures. On March 21, city officials extended some emergency measures for an additional 3 weeks, including traffic restrictions and curfews, although city residents, hotel guests, and local employees are exempt.  

NEW ZEALAND CONSIDERS “TRAVEL BUBBLE” New Zealand’s COVID-19 control strategy has received praise as one of the most effective in the world. Neighboring Australia has shown similar effectiveness in controlling COVID-19, prompting the two countries to consider creating a COVID-19 bubble for air travel. The so-called “trans-Tasman travel bubble” would allow travelers to skip 14-day quarantine measures. Ideally, the travel bubble would consist of shared protocols, detailed plans for isolation facilities, and contact tracing; however, plans for the travel network have not been finalized.New Zealand Prime Minister Jacinda Ardern postponed an announcement for a definitive launch date until April 6.

A study by New Zealand public health officials, published in the US CDC’s Emerging Infectious Diseases (EID) journal, outlines an outbreak investigation in September 2020 originating from an international flight from India to New Zealand. At least 6 passengers tested positive in the managed quarantine and isolation facility or following the completion of their 14-day quarantine. Using genomic analysis and standard contact tracing, the authors hypothesized that transmission occurred during the quarantine period, including between individuals with no direct contact. The case investigators demonstrated that SARS-CoV-2 transmission on international flights can be successfully traced and managed, which will be critical if travelers in the bubble can forgo the quarantine period.

GLOBAL VACCINE COORDINATION Earlier this month, COVAX shipped some of their first COVID-19 vaccine doses to almost 30 different countries. An editorial in The Lancet and a letter in The BMJ raised the idea of appointing a Global Vaccine Coordinator, who would lead an international effort for the equitable distribution of vaccines. The authors argue that clear leadership and oversight are needed to organize what has become largely a piecemeal vaccination effort, with nations, NGOs, and the private sector working independently or bilaterally. While a centralized global champion or body could provide high-level coordination for global vaccine allocation and distribution, it would be a major challenge to ensure they have the authority necessary to compel national governments and private sector companies to participate.

MATERNAL AND NEWBORN IMMUNITY Previously published research has already provided evidence that seropositive pregnant mothers can transfer SARS-CoV-2 antibodies to their fetus via the placenta, based on IgG antibodies detected in umbilical cord blood. Now, pre-prints and new publications are supporting the notion that this phenomenon also may be true in vaccinated pregnant women, with SARS-CoV-2-specific antibodies present in both breast milk and cord blood.

A prospective cohort study (preprint) investigated the effects of COVID-19 mRNA vaccination on pregnant and lactating women, including immunogenicity, reactogenicity, and presence of vaccine-generated antibodies in umbilical cord blood and breast milk samples. The researchers found that vaccine-generated antibodies were present across all samples of umbilical cord sera and breast milk, when compared with baseline samples. The effect was also dose dependent, with detectable SARS-CoV-2-specific IgG increasing in cord blood and breast milk after administration of the second dose. Researchers from Florida Atlantic University (US) published a case report in BMC: Pediatrics documenting the first known presence of vaccine-induced SARS-CoV-2 IgG antibodies in cord blood. The antibodies were detected in the cord blood for an infant born to a mother who received the first dose of the Moderna vaccine 3 weeks before delivery.

SEROPREVALENCE AND IMMUNITY IN WUHAN In a study published in The Lancet, Chinese researchers estimate the burden of SARS-CoV-2 infection during the initial COVID-19 outbreak in Wuhan, China. They performed a cross-sectional analysis of seropositivity for SARS-CoV-2 antibodies in 9,702 individuals who reported living in Wuhan during December 2019. Initial blood specimens were collected in April 2020, and subsequent specimens were collected in June and October 2020. The researchers estimate a seroprevalence of 6.92% in their study population. Notably, 82% who were seropositive were asymptomatic during the study period.

In an associated commentary, experts from the University of Melbourne (Australia) point out that this seroprevalence estimate would equate to more than 622,000 COVID-19 cases during the initial outbreak if applied to the entire Wuhan population, far more cases than were reported in April 2020 (50,333 as of April 17). The commentary authors hypothesize that the discrepancy could be due to high levels of asymptomatic infection and transmission or potentially underreporting, which could also be impacted by high proportions of asymptomatic infections. Of the 6.92% of seropositive participants, approximately 39.8% were positive for neutralizing antibodies at the baseline visit in April 2020, and this value persisted throughout the study period, which provides evidence of protective immunity conferred through natural infection. With less than half of this population showing protective immunity, the authors underscore the importance of mass vaccination campaigns to prevent future infections and reinfections.   

REINFECTION RISK Researchers in Denmark found that natural infection confers lasting immunity against SARS-CoV-2, but to a lesser degree in older adults. The study, published in The Lancet, included data from more than 500,000 individuals during Denmark’s first surge, including 11,068 who tested positive. Among those who tested positive, 72 tested positive again at least 90 days later, compared to 16,819 who tested negative. This corresponds to 80.5% protection against reinfection. A secondary cohort analysis of more than 2.4 million individuals found similar overall results (78.8% protection), but lower protection (47.1%) in adults aged 65 years and older.

A study by researchers at the Cleveland Clinic (Ohio, US), published in Clinical Infectious Diseases, found similar levels of protection. The study included test data from more than 150,000 patients tested prior to August 30, 2020, including 8,845 who tested positive. Among the positive patients, 1,278 were retested at least 90 days later, and the researchers identified 63 possible reinfections (31 symptomatic). The researchers estimate 81.8% protection against reinfection.

Both studies acknowledge that PCR tests can be positive for prolonged periods of time following the resolution of acute infection, due to persistent fragments of SARS-CoV-2 RNA, but these studies provide further evidence regarding the degree of protection conferred by natural infection and help characterize the risk of reinfection.

COVID-19 TESTING TOOLKIT WEBINAR The Johns Hopkins Center for Health Security is launching a new informational webinar series on SARS-CoV-2 testing strategies and best practices from selected organizational leaders. This webinar series will be hosted as part of the Center’s new COVID-19 Testing Toolkit, which aims to provide essential information for all organizations seeking to engage in SARS-CoV-2 testing.

This first webinar, held on March 24 at 11am EDT, will feature a conversation with Ginkgo Bioworks on how they launched their innovative SARS-CoV-2 testing service, Concentric by Ginkgo, and their efforts to pilot the program in schools. The panelists will discuss the importance of testing to mitigate COVID-19 risk as schools resume in-person classes as well as the role of biotechnology in countering future outbreaks and pandemics. Register for the webinar here.