expert advice on corona virous on january 2021

 

EPI UPDATE The WHO COVID-19 Dashboard reports 102.94 million cases and 2.23 million deaths as of 11am EST on February 2. The weekly global incidence decreased for the third consecutive week, down to 3.63 million new cases. This is a decrease of nearly 15% compared to the previous week, and it is the lowest weekly total since late October. Weekly global mortality also decreased nearly 4% compared to the previous week, down to 93,803 deaths. Considering the reporting interruptions over the winter holidays, it is unclear exactly when the actual global incidence peaked; however, the decrease in mortality could be an early indication of a longer-term trend corresponding to decreases in incidence starting 2-4 weeks ago.

Our World in Data reports that 101.31 million vaccine doses have been administered globally, a 48% increase since this time last week.

UNITED STATES

The US CDC reported 26.03 million total cases and 439,955 deaths. The US is currently averaging 3,145 deaths per day, and it could surpass 450,000 cumulative deaths in the next 3-4 days.

National-level daily incidence continues to decrease, down from nearly 250,000 new cases in per day in mid-January to around 150,000. While the daily incidence continues to decrease, the current average is still more than double the peak of the summer surge. Daily mortality is also beginning to show signs of declining. The US has reported decreasing daily mortality for 5 consecutive days, down 5% since January 26. Additional data are needed to determine if this is an early indication of a longer-term trend, but a decrease spanning multiple days is an encouraging sign.

US Vaccination

The US CDC reported 49.94 million vaccine doses distributed and 32.22 million doses administered. The US has administered 64.5% of the distributed doses, which is an increase of more than 10 percentage points from Friday’s update (54.1%). In total, 26.02 million people (approximately 7.9% of the US population) have received at least 1 dose of the vaccine, and 5.93 million (1.8%) have received both doses. The US is now averaging 1.36 million doses administered per day, a 20% increase from the previous week. The breakdown of doses by manufacturer remains relatively even, with slightly more Pfizer/BioNTech doses administered (17.36 million; 54%) than Moderna (14.76 million; 46%).

The CDC moved data for vaccination at long-term care facilities (LTCF) to its own dashboard. A total of 3.75 million doses have been administered through the Federal Pharmacy Partnership for Long-term Care Program*, covering 3.14 million individuals with at least 1 dose and 594,857 with 2 doses. The dashboard breaks down the doses by those administered to LTCF residents and those administered to staff. Based on the available data, approximately 60% of the doses have gone to residents and 40% to staff.

*The dashboard only includes data for doses administered through the federal program. It does not report data from West Virginia, which opted out of the program.

The Johns Hopkins CSSE dashboard reported 26.35 million US cases and 444,336 deaths as of 1:30pm EST on February 2.

RUSSIAN VACCINE Sputnik V, Russia’s primary vaccine candidate, appears to be safe and effective in preventing symptomatic COVID-19, based on preliminary analysis of Phase 3 clinical trial data published in The Lancet. The clinical trials included nearly 20,000 participants, with 75% randomly assigned to receive the vaccine. The researchers identified 16 cases of COVID-19 among the treatment group (14,964 participants) and 62 cases among the placebo group (4,902), corresponding to an overall efficacy of 91.6% in terms of preventing COVID-19 disease, similar to the results for the Pfizer-BioNTech and Moderna vaccines. Notably, the vaccine also exhibited 91.8% efficacy among adults over the age of 60, and no moderate or severe cases of COVID-19 were reported among the vaccinated participants. No serious adverse events were determined to be associated with the vaccine.

The Sputnik V vaccine is administered in 2 doses, administered 21 days apart. It requires the temperature to be maintained at approximately 0°F (-18°C), with short-term storage at 36-46°F (2-8°C). In contrast, ultra-cold storage (approximately -80°F or -62°C) is required for the Pfizer-BioNTech vaccine.

The Russian government came under criticism in August 2020 after making the Sputnik V vaccine candidate available to the public before Phase 3 clinical trials were completed. More than a dozen other countries have already authorized the use of the Sputnik V vaccine. 

US VACCINATION The US CDC COVID-19 Response Team published data from the early stages of SARS-CoV-2 vaccination efforts in the US. The first study, published in the CDC’s MMWR, described demographic characteristics among those vaccinated in the first month—December 14, 2020 to January 14, 2021. The researchers analyzed age, sex, and race/ethnicity data for nearly 13 million individuals who received at least 1 dose of the vaccine. The majority of those vaccinated were older adults, with 55% aged 50 years and older, including 13.4% aged 65-74 years and 15.6% aged 75 years and older. Additionally, 63% of those vaccinated were female.

Among 6.7 million individuals with race/ethnicity data, the majority (60.4%) were White*, compared to 11.5% Hispanic/Latinx, 5.4% Black*, 6.0% Asian*, and 2.3% American Indian, Alaskan Native, Native Hawaiian, or Other Pacific Islander* and 14.4% were listed as Multiple races/ethnicities or Other. The researchers indicate that the demographic distributions appear to largely reflect those of the earliest priority populations outlined by the CDC’s Advisory Committee on Immunization Practices, including LTCF residents and healthcare workers. Notably, however, the proportion of Black vaccinees was lower than would be expected considering the racial/ethnic distribution these priority groups.

*Non-Hispanic.

The second article, also published in the CDC’s MMWR, discussed vaccination coverage among LTCF residents and staff. The researchers evaluated data on nearly 1.3 million individuals vaccinated through the CDC Pharmacy Partnership for Long-Term Care Program from December 18, 2020 to January 17, 2021. Among these individuals, 713,909 were residents and 582,104 were facility staff. In total 12,702 facilities participated in the program, of which 11,460 (90.2%) conducted at least one on-site vaccination clinic. This effort provided at least 1 dose of the vaccine to an estimated 77.8% of residents at these facilities, but only 37.5% of staff. Due to a combination of factors—including age, underlying health conditions, and prolonged close contact in congregate settings—LTCF residents are at elevated risk for infection, severe disease, and death, so it is important to achieve high vaccination coverage at these facilities.

In addition to state and local governments, tribal nations are also scaling up vaccination efforts. The Navajo Nation, one of the most severely affected tribal nations during the US epidemic (29,860 cases), eased its weekend curfew in an effort to expand vaccination. The principal challenges are addressing vaccine hesitancy, particularly among older adults who are at elevated risk, and reaching individuals who live in rural areas that are unable or unwilling to travel to get vaccinated, especially during adverse winter weather conditions. Proactive effort by tribal leadership and health workers has driven substantial progress in terms of vaccination coverage. To date, Navajo Nation has administered at least 1 dose of SARS-CoV-2 vaccine to more than 20% of its population, higher coverage than any US state or territory.

VACCINATION PROTESTS Dodger Stadium in Los Angeles, California, is currently serving as one of the largest mass vaccination sites in the US, but protests by anti-vaccination groups caused the site to be temporarily shut down on Saturday when protesters blocked the entrance to the stadium. Fortunately, the disruption did not result in the cancellation of any appointments, but Governor Gavin Newsom emphasized that protests will not be deterred by protests. Protesters reportedly attempted to intimidate individuals waiting in line and spread misinformation about COVID-19 and the vaccine. New safety measures at Dodger Stadium will clearly delineate where protesters are permitted to be in order to prevent further disruptions to vaccination operations. 

GERMANY On January 29, the European Commission issued a conditional marketing authorization (CMA) for the use of the AstraZeneca-Oxford University SARS-CoV-2 vaccine in adults aged 18 and older. While the announcement acknowledged that the clinical trials primarily included adults aged 18-55 years, the CMA did not include an upper age limit. In a decision stemming from a concern about insufficient efficacy data in older adults, Germany authorized the AstraZeneca-Oxford vaccine only for adults aged 18-64. Currently, vaccine eligibility in Germany is limited to residents and staff of long-term care facilities, adults aged 80 years and older, and frontline healthcare workers. Because the AstraZeneca-Oxford vaccine is not authorized for many high-risk individuals due to Germany’s age restrictions, Germany will reportedly review its eligible populations and prioritize use of that particular vaccine in younger healthcare workers and LTCF staff.

Germany has struggled with a slow start to its vaccination campaign, and Chancellor Angela Merkel reportedly met with state governors, EU leadership, and representatives from the pharmaceutical industry yesterday to identify mechanisms to speed progress toward national vaccination coverage. Following the meeting, Chancellor Merkel indicated that Germany still anticipates being able to vaccinate its entire population by September 2021, even if no additional vaccines are authorized for use.

Like many countries around the world, Germany recently instituted travel restrictions in response to emerging, highly transmissible SARS-CoV-2 variants. Notably, non-German citizens arriving from “areas of variant of concern”—currently Brazil, Eswatini, Ireland, Lesotho, Portugal, South Africa, and the UK—will not be permitted to enter the country, even with a recent negative SARS-CoV-2 test. Individuals who are eligible to enter—including German citizens and residents—and recent travel to “high incidence areas” or “virus variant areas” must provide proof of a negative test prior to entry, and all individuals with recent travel to “risk areas”—which covers most countries, including most in Europe—must be tested within 48 hours after arrival. All travelers arriving from places identified as at risk, high-incidence, or variant areas are required to self-quarantine for 10 days after they arrive. The quarantine can potentially be terminated after 5 days, with a negative test. The new restrictions are expected to remain in place through at least February 17.

DRC DRONE VACCINE DISTRIBUTION Drones have previously been used for the delivery of medical supplies, including vaccines, to areas that are remote or difficult to access. The Democratic Republic of the Congo (DRC) recently announced a partnership between VillageReach, Swoop Aero, and the DRC Ministry of Health—“Drones for Health”—will use drone to promote equitable access to healthcare for half a million people in remote communities of the Equateur province. In addition to standard medical supplies, the new program is expected to support SARS-CoV-2 vaccination efforts in the country. These drones will be used to deliver medicine and other supplies to 75 health facilities in the province. 

REFUGEES & DISPLACED POPULATIONS Refugees are among the most vulnerable populations in the world, particularly in the midst of a pandemic. Being displaced from their homes and separated from community support systems, refugees and other displaced populations often live in congregate settings without access to clean water or proper sanitary equipment, which exacerbates risk of transmission and severe disease. Furthermore, displaced populations face significant barriers in terms of accessing healthcare, and medical organizations that work with these populations are often underfunded and overwhelmed. King Abdullah II Ibn Al Hussein of Jordan recently announced that the Jordanian government initiated vaccination operations for refugee population in the country. King Abdullah viewed it as part of Jordan’s “global responsibility” and “moral duty” to protect the most vulnerable from COVID-19. The UN Refugee Agency (UNHCR) applauded Jordan’s initiative to include displaced populations in its vaccination program and encouraged other countries to follow Jordan’s example.

In recognition of the disproportionate COVID-19 burden among immigrant populations, many of whom are racial and ethnic minorities, the US Department of Homeland Security (DHS) is committing resources to ensure equal access to SARS-CoV-2 vaccines for undocumented immigrants. A statement issued by DHS emphasized the “public health imperative” in ensuring access to vaccination, regardless of immigration status. While many undocumented immigrants are not refugees, they may face similar stigma and barriers to accessing public health and healthcare. As part of this effort, the Federal Emergency Management Agency will coordinate vaccination clinics that aim to reach “underserved and rural communities,” and federal immigration officials, including Immigration and Customs Enforcement and Customs and Border Protection, “will not conduct enforcement operations at or near vaccine distribution sites or clinics” in order to encourage participation by vulnerable individuals and communities.

PREGNANT WOMEN On January 26, the WHO updated its guidance on the Moderna SARS-CoV-2 vaccine to include pregnant women. Previously, the WHO recommended against vaccinating pregnant women unless they were at elevated risk, which conflicted with recommendations published by the US CDC. While the current iterations of both sets of guidelines do not explicitly recommend vaccinating pregnant women, both note that there is currently no evidence to suggest that the vaccine poses safety concerns for pregnant women.

A study published in JAMA: Pediatrics provides evidence that pregnant women may be able to pass IgG antibodies against SARS-CoV-2 to their fetus. The study involved 1,417 women who recently gave birth. Among 83 mothers with detectable SARS-CoV-2 antibodies, 72 (86.7%) transferred IgG antibodies to their fetus—as detected in the newborns’ cord blood. IgM antibodies were not detected in any cord blood specimens, and antibodies were not detected in any infants born to mothers without detectable antibodies. The concentration of antibodies in the cord blood was significantly correlated with the concentration in the mother, but the antibodies were successfully transferred by mothers who exhibited symptomatic disease and asymptomatic infection. The study did not explicitly evaluate the ability to transfer antibodies developed as a result of vaccination; however, the researchers indicate that the results align with similar studies on transplacental transfer of vaccine-conferred antibodies for other diseases. Further research is necessary to determine the recommended timing for vaccination of pregnant women in order to achieve sufficient transplacental transfer of SARS-CoV-2 antibodies to the fetus.

US ECONOMIC STIMULUS With the Democratic party now in control of the US House of Representatives, Senate, and White House, pressure is increasing to negotiate additional federal economic relief for the COVID-19 epidemic. US President Joe Biden announced his proposal for a new COVID-19 economic stimulus and recovery package, the American Rescue Plan, which includes US$1.9 trillion in funding. The package includes support for SARS-CoV-2 testing and vaccination efforts ($415 million) and small businesses ($440 million). It also includes $1 trillion in direct support for individuals and families, including another round of stimulus checks and increased and extended unemployment benefits. Additionally, the package includes broader provisions to increase the federal minimum wage and expand access to affordable childcare and healthcare.

While the Democratic party holds a majority in the Senate (with the tie-breaking vote from Vice President Kamala Harris), there are limited options available to pass a funding bill without some degree of Republican support. In hopes of stimulating bipartisan negotiations, 10 Republican Senators visited the White House to outline an alternate funding package, which totals $618 billion. The Republican proposal would include smaller and more targeted direct stimulus checks for individuals; maintain the current $300 federal supplemental unemployment benefits through June, as opposed to $400 through September in the White House plan; and reduce support for schools from $170 billion in the White House plan to $20 billion. The Republican plan would also eliminate funding to expand the national public health workforce; $350 billion in support to state, local, and tribal governments; subsidies for health insurance premiums; and the minimum wage increase. The initial meeting was reportedly productive, and there appears to be interest on both sides to continue negotiations.

As we have covered previously, the large-scale response efforts in many jurisdictions—including testing, surveillance, and vaccination—have posed major financial challenges to jurisdictions across the country. An investigation by STAT News found that senior US government officials under the Trump Administration “actively lobbied Congress to deny state governments any extra funding for the Covid-19 vaccine rollout.” STAT News reports that the primary point of contention reportedly dealt with the speed with which states were using previous federal funding allocations for COVID-19 response.

EMERGING VARIANTS As scientists continue to monitor emerging SARS-CoV-2 variants of concern (VOCs), researchers are identifying new mutations. Of particular concern is the E484K mutation, which consists of an amino acid change in the spike receptor binding domain of the SARS-CoV-2 virus. This change appears to result in increased binding strength of the spike protein to the ACE2 receptor, which is how the virus enters human cells. Notably, the E484K mutation appears to result in increased transmissibility and resistance to monoclonal antibody treatments. This mutation has been identified in several variants of SARS-CoV-2 in different geographic areas, including Brazil and the UK, and it appears to be increasing in prevalence, which suggests increased fitness compared to other mutations. The fact that this mutation has been independently acquired in multiple locations and variants indicates that the E484K changes in the spike gene are broadly advantageous to SARS-CoV-2 and may continue to arise in subsequent variants. 

Aside from the E484K mutation, scientists monitoring the B.1.1.7 VOC also must track its prevalence and incidence among the population. Since whole genome sequencing to detect the Δ69-70 mutation is costly and time consuming, the UK’s NERVTAG expert group used existing laboratory PCR-based testing to track the variant. Specifically, the Δ69-70 mutation in the spike gene causes S gene target failure (SGTF) in the ThermoFisher TaqPath assay, resulting in a false negative PCR test from a known positive sample. By looking for SGTF in known positive samples (confirmed by other PCR assays), researchers can monitor the extent of the Δ69-70 mutation in the B.1.1.7 VOC without the need for time- and resource-intensive whole genome sequencing methods.

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 from CommuniVax, 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 101.05 million cases and 2.18 million deaths as of 1pm EST on January 29. The global cumulative incidence surpassed 100 million cases on January 28. 1 case to 20 million: 220 days 20 to 40 million: 68 days 40 to 60 million: 38 days 60 to 80 million: 32 days 80 to 100 million: 32 days On January 23, the United Kingdom surpassed 100,000 cumulative deaths*, and Mexico surpassed 150,000 cumulative deaths on January 25. With these milestones in mind, we will take another look at national-level cumulative COVID-19 mortality data. *Deaths within 28 days of a positive SARS-CoV-2 test. In terms of total cumulative mortality, the UK (104,371) is currently #5 globally, and Mexico (155,145) is #4. The United States (427,626 deaths), Brazil (221,547), and India (154,010) represent the top 3. In total, 12 countries have reported more than 50,000 cumulative deaths, including 6 in Europe, 4 in the Americas, 1 Asia, and 1 in the Eastern Mediterranean region. Together, these 12 countries account for 70% of the total global deaths. A total of 133 countries and territories (of 179 total) have reported fewer than 5,000 cumulative deaths, including 91 with fewer than 1,000 and 38 with fewer than 100. In terms of per capita mortality, there are 28 countries with more than 1,000 cumulative deaths per million population, which corresponds to more than 1 death for every 1,000 people. San Marino is #1 with 1,915, followed by #2 Belgium (1,810) and #3 Slovenia (1,658). The US is #10 with 1,309 deaths per million. Of these 28 countries, 21 are in Europe, and 7 are in the Americas. The global average is 279.63 cumulative deaths per million population. At the other end of the spectrum, 86 countries and territories have reported fewer than 100 deaths per million. Additionally, 30 countries and territories have reported fewer than 10 deaths per million, and 9 have reported fewer than 2. Our World in Data reports that 86.14 million vaccine doses have been administered globally, a 50% increase since this time last week. UNITED STATES The US CDC reported 25.46 million total cases and 427,626 deaths. Daily incidence continues to decrease, down to 161,832, the lowest average since November 17* and 35% lower than the peak on January 8 (248,706). *Excluding the week after Thanksgiving, during which the average was depressed due to delayed holiday reporting. Yesterday, the US daily mortality returned to approximately 3,300 deaths per day. Overall, the daily mortality has remained relatively consistent for more than 2 weeks. Whether steady at approximately 3,300 or 3,100** deaths per day, the overall daily mortality has not fluctuated much from day to day since mid-January. Daily incidence continues to decrease, and it likely peaked somewhere between mid-December and mid-January—although difficult to determine exactly when due to fluctuations in reporting around the winter holidays. If this is the case, we expect to observe an associated decrease in daily mortality starting sometime in the next week or two. **During the week following the Martin Luther King, Jr. Day holiday weekend, the average daily mortality dropped from approximately 3,300 to 3,100 deaths per day due to delayed reporting over the holiday weekend; however, even with this decrease, the daily mortality remained relatively constant until it increased again to 3,300. The US CDC reported 48.39 million vaccine doses distributed and 26.19 million doses administered, including 3.10 million administered in long-term care facilities (LTCFs). The US has administered 54.1% of the distributed doses, which is actually a slight decrease from Monday’s update (54.9%). In total, 21.70 million people have received at least 1 dose of the vaccine, and 4.26 million have received both doses. The US is now averaging 1.24 million doses administered per day. The breakdown of doses by manufacturer remains relatively even, with slightly more Pfizer/BioNTech doses administered (14.36 million; 55%) than Moderna (11.74 million; 45%). The Johns Hopkins CSSE dashboard reported 25.84 million US cases and 434,696 deaths as of 2:30pm EST on January 29. US VACCINATION STRATEGY The US is continuing to adapt its SARS-CoV-2 vaccination strategy as the new presidential administration settles into office. Earlier this week, US President Joe Biden expressed confidence that the US will have enough supply to vaccinate 300 million individuals by the end of the summer. As part of this effort the federal government is negotiating the purchase of approximately more 200 million doses, 100 million each of the Pfizer/BioNTech and Moderna vaccines. Despite plans to scale up supply and distribution, the White House’s COVID-19 response team is calling for patience from the American people, noting that it will likely be months before everyone who would like a vaccine can get one. The administration is currently on track to meet its goal of vaccinating 100 million individuals in the first 100 days after President Biden took office. Even with increased supply and distribution, a number of barriers remain to vaccinating the US population. Notably, the absence of a federal vaccine stockpile has led states to reserve half of their allocation to ensure enough supply for second doses, which is slowing vaccination efforts. Until states can have confidence in longer-term planning for vaccine deliveries, many will likely continue to reserve doses. Additionally, some of the world’s largest syringe manufacturers warn that the demand for specialized syringes—such as the low-dead volume syringes—may soon exceed production capacity. Without the low-dead volume syringes, vaccinators may not be able to draw extra doses from each vial, which could reduce the number of available doses by 17%. In an effort to support states’ vaccination operations, the Department of Defense is reportedly evaluating plans to use military personnel to supplement vaccinators. The plan could deploy military personnel domestically to assist in the logistics and vaccine administration at federal vaccination sites. FEMA intends to establish 100 vaccination sites nationwide in the coming months, but any deployment of active duty military personnel would require approval by state governments. VACCINES & ALLERGIC REACTIONS The US CDC published new data on the incidence of allergic reactions following vaccination. The CDC reported 50 incidents of anaphylaxis after vaccination with the Pfizer product and 21 instances after receiving the Moderna vaccine, which corresponds to approximately 5 reactions per million doses for the Pfizer vaccine and 2.8 per million doses for the Moderna vaccine. Notably, the rate for the Pfizer vaccine is less than half what it was in late December (11.1 per million), although the rate for the Moderna vaccine increased slightly compared to the data reported through January 10 (2.5 per million). To date the CDC has reported no deaths due to an allergic reaction following vaccination.  EMERGING VARIANTS The recently discovered SARS-CoV-2 variants of concern continue to spread around the world. The B.1.351 variant was identified in South Carolina this week, the first time the variant has been reported in the US. The variant was identified in 2 patients with no known international travel history, and notably, there is “no known connection between these two cases.” This provides a good indication that the variant is already circulating in the community. The B.1.351 variant has already been identified in 30 countries, and has recently garnered attention due to its potential to reduce the effectiveness of SARS-CoV-2 vaccines. The absence of large-scale genomic sequencing efforts in the US has left the country more vulnerable to the spread of these new SARS-CoV-2 variants, and many health experts have called for national programs to enhance domestic sequencing capabilities. Currently, approximately 3,000 specimens are sequenced each week, out of 1.4 million positive tests. These efforts are principally led by “a patchwork of academic, state and commercial laboratories” rather than a formal, centralized, and coordinated national system. Coverage by existing sequencing efforts varies widely by state, with some states reporting no sequencing data at all during the pandemic. Without proactive efforts to sequence specimens collected across the country, there is no effective way to identify the emergence or introduction of new variants or monitor their geographic spread. ASTRAZENECA/OXFORD VACCINE After receiving the application for conditional authorization of the AstraZeneca/Oxford University vaccine on January 12, the European Medicines Agency (EMA) issued its recommendation today that the vaccine receive conditional marketing authorization in Europe. Prior to the EMA’s assessment, German officials called for the vaccine to be authorized only for adults under the age of 65, due to a dearth of efficacy data among older adults. German officials emphasized that there are no data suggesting that the vaccine is less efficacious in this age group, but rather, that the efficacy data are not sufficient to make a determination. The vaccine is already being administered in the UK, including to adults 65 years and older, and UK officials indicate that there is no evidence that the vaccine is less effective in older adults. German officials expected the EMA to include an age restriction in its recommendation, but the EMA recommendation did not include a maximum age limit. In addition to concerns regarding the AstraZeneca/Oxford vaccine’s efficacy, AstraZeneca announced that production is lower than anticipated and that it will be unable to deliver the full order to the EU on time, potentially only 25% of the total doses by the end of March. The shortfall raised concerns that doses that should have been allocated to the EU were being sold to other countries. Officials from the European Commission have demanded AstraZeneca meet its commitment to the EU, even if it means diverting doses from the UK. Driven by the situation with AstraZeneca, the European Commission is implementing an “export transparency mechanism” for SARS-CoV-2 vaccines manufactured in the EU, which will require permission before exporting doses for sale. Humanitarian donations would not be affected. There are currently 2 facilities in the EU that are manufacturing the AstraZeneca/Oxford vaccine, but it remains to be seen how the new transparency measure would ultimately affect allocation of vaccine doses produced within the EU. J&J/JANSSEN VACCINE Johnson & Johnson (J&J) announced interim efficacy data from the Phase 3 clinical trials of its SARS-CoV-2 vaccine candidate, developed in partnership with Janssen Pharmaceuticals. Overall, the vaccine demonstrated 66% efficacy in preventing moderate-to-severe COVID-19 disease across several trial locations: the US (72%), Latin America (66%), and South Africa (57%). The lower efficacy in Latin America and South Africa prompted concern about the vaccine’s protection against emerging variants, including B.1.351 which is circulating widely in South Africa. Notably, the J&J press release indicated that “nearly all cases of COVID-19 (95%) [in South Africa] were due to infection with...the B.1.351 lineage.” The vaccine demonstrated 85% efficacy in terms of preventing severe disease across all locations, regardless of the variant. Additionally, J&J noted that the vaccine “demonstrated complete protection against COVID-related hospitalization and death” after 28 days post-vaccination. The Phase 3 trials included nearly 44,000 participants across 8 countries on 3 continents. A study of the vaccine using 2 doses is still underway. In contrast to the existing SARS-CoV-2 vaccines, the J&J/Janssen vaccine requires only a single dose, so while the efficacy is lower than for other products, it could provide benefit in terms of accelerating vaccination coverage. Additionally, it can be stored for up to 3 months at refrigerator temperature (ie, 35.6-46.4°F; 2-8°C). J&J intends to submit its application for Emergency Use Authorization (EUA) to the US FDA in “early February” with the goal of having supply available to distribute immediately. Even without efficacy in the 90%+ range, the J&J/Janssen is expected to be another valuable tool in combating COVID-19. The results were published via press release, and to our knowledge, the trial data have not been published publicly or subjected to peer review; however, J&J committed to submitting “a comprehensive...data set” to a peer-reviewed journal in the near future. NOVAVAX VACCINE Novavax issued a press release with preliminary Phase 2b and Phase 3 clinical trial results for its candidate SARS-CoV-2 vaccine. The vaccine demonstrated an overall efficacy of 89.3% in Phase 3 trials conducted in the UK. The UK trials included more than 15,000 participants, and of the 62 cases reported, 56 were in the placebo group, and 61 were mild or moderate cases. The only severe case was among the placebo group. Of 56 infections that were sequenced, 32 (57%) were due to the B.1.1.7 variant*. Further analysis indicates that the vaccine demonstrated 95.6% efficacy against the original strain and 85.6% against the B.1.1.7 variant. *Described in the press release as the “UK variant strain,” which we presume to mean the B.1.1.7 variant, which was first reported in the UK. Novavax also reported interim results from Phase 2b clinical trials in South Africa. Overall, the vaccine demonstrated 60% efficacy in preventing mild, moderate, or severe disease in HIV-negative participants (49.4% efficacy in HIV-positive participants). Sequencing data are available for 27 or 44 total cases, and 25 (92.6%) of the infections were due to the B.1.351 variant**. **Described in the press release as “the triple mutant variant...widely circulating in South Africa,” which we presume to mean the B.1.351 variant, which was first reported in South Africa. The underlying data for these results have not yet been published publicly or subjected to peer review, but Novavax intends to publish them via “prepublication servers” and submit them to a peer-reviewed journal. Additionally, Novavax is submitting data on a rolling basis to the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) in order to streamline the review process. In addition to these trials, further Phase 3 trials are ongoing in the US and Mexico, which have enrolled more than 16,000 of the target 30,000 participants. The timeline for completing the US-Mexico trials or submitting an EUA application to the US FDA remains uncertain. Like existing SARS-CoV-2 vaccines, the Novavax candidate requires 2 doses, administered 21 days apart, although it can be stored for a prolonged period (6 months minimum) at refrigerator temperatures (ie, 35.6-46.4°F; 2-8°C)—and even 24 hours at room temperature—which will facilitate distribution and storage at the local level. While the vaccine appears to be less efficacious against the B.1.351 strain, Novavax is reportedly already developing a new version of the vaccine to better protect against the emerging variant.  DOUBLE MASKING The idea of “double masking”—ie, wearing 2 masks on top of one another rather than a single mask—has emerged over the past week or so in the US. The idea itself is not new, but it gained attention following recent comments by Dr. Anthony Fauci in support of wearing multiple masks. Dr. Fauci’s comments reference emerging SARS-CoV-2 variants that appear to be more transmissible than those circulating earlier in the pandemic, which could necessitate enhanced risk mitigation measures to sufficiently reduce transmission risk. Wearing an extra mask aims to provide additional layers of filtration for inhaled and exhaled air with the ultimate goal of further decreasing SARS-CoV-2 transmission risk. Dr. Fauci stated that the benefit of double masking is “common sense,” but to our knowledge, the evidence supporting increased effectiveness is limited. Masks can vary considerably—including in terms of design, construction, materials, and fit—which make it difficult to accurately determine any increase in the effect of adding subsequent masks. Notably, the US CDC already recommends selecting a mask constructed with multiple layers. It is well established that face masks and coverings can reduce transmission risk, if used properly, and we continue to recommend following the CDC guidance regarding face coverings, particularly when appropriate physical distancing cannot be maintained. We will continue to monitor emerging evidence and guidance regarding double masking. EUROPE CONTROL MEASURES Despite vaccination struggles, some countries in Europe are beginning to evaluate and implement steps to ease COVID-19 restrictions. England’s current national “lockdown” is scheduled to continue through March 8, and UK Prime Minister Boris Johnson indicated that in-person education will not resume before then, and the ultimate decision could hinge on vaccination progress. The UK aims to complete the first dose of vaccine for its highest-priority populations by February 15. England could begin phasing out the lockdown beginning the week of February 22, but nonessential shops, pubs, and restaurants are expected to remain closed into March. In addition to domestic restrictions, arriving international travelers from 22 hotspot countries, including South Africa and all of South America, will be required to quarantine for 10 days upon arrival, over concerns regarding highly transmissible emerging variants.  After 3 weeks of national “lockdown,” Cyprus will begin loosening restrictions in early February. Cyprus’ Minister of Health, Constantinos Ioannou, announced that the country would begin easing restrictions starting February 1. The efforts will reportedly begin with “hair and beauty salons,” followed by retail stores and elementary schools. Cyprus will maintain some restrictions, such as limits on large gatherings—including for religious services—and mandatory notification (via text message) before leaving one’s home, in order to mitigate the risk of increasing social activity too rapidly. AFRICA The Africa CDC announced that it secured another 400 million doses of the AstraZeneca/Oxford vaccine, manufactured by India’s Serum Institute. This adds to the 270 million doses previously secured from Pfizer, AstraZeneca, and Johnson & Johnson (J&J). Countries in Africa are also expected to receive 600 million doses through the WHO’s COVAX initiative, which could ultimately provide enough vaccine to cover 2 doses for more than 600 million people—approximately half of the continent’s 1.2 billion people. A WHO spokesperson remarked that vaccinating 35% of Africa’s population by the end of 2021 is a “realistic assumption,” but many obstacles remain. In addition to vaccine supply and distribution, acceptance remains a problem in many countries, compounded by widespread misinformation. For example, Tanzanian President John Magufuli openly opposes the SARS-CoV-2 vaccines He has claimed that Tanzanians will be used as “guinea pigs,” and he has already declared COVID-19 to be eliminated in the country. Notably, Tanzania has not reported COVID-19 data since April 2020, when it reported only 509 cumulative cases. While African countries struggle to secure enough doses of vaccine to protect their populations, many across the continent are also struggling with a surge of transmission and increased mortality. Dr. John Nkengasong, Director of the Africa CDC, noted that health systems in Africa are becoming overwhelmed by the current surge, which may be exacerbated by the emergence of highly transmissible variants, including B.1.351. To date, only 2 countries in sub-Saharan Africa—Mauritius and Seychelles—have commenced vaccination efforts. While many African nations managed to contain COVID-19 throughout 2020, the ongoing surge is a reminder that no country is safe from the pandemic, and without access to critical vaccine supply—which is largely limited to higher-income countries for now—fragile public health and healthcare systems in Africa could be at risk. MANAUS, BRAZIL A study published in The Lancet analyzed the increased SARS-CoV-2 transmission in Manaus, Brazil, a region that had previously shown high levels of seroprevalence among its community members. A study conducted in October 2020 detected SARS-CoV-2 antibodies in samples from 76% of blood donors, which suggested that the region may have reached the threshold to provide some level of community immunity (ie, herd immunity). Despite the high seroprevalence, Manaus exhibited a large surge in COVID-19 cases and hospitalizations in January 2021. The researchers present 4 possible explanations for the surprising surge in cases. First, the previous study could have overestimated the seroprevalence, which could have put the community below the herd immunity threshold. Second, immunity to SARS-CoV-2 conferred by earlier infection could have waned, resulting in re-infections. Third, the new infectious could be a result of emerging variants, including the P.1 variant first reported in the area, that are less susceptible to antibodies from prior infections. And finally, new SARS-CoV-2 lineages could simply be exhibiting much higher transmissibility, which could allow widespread community transmission even in areas with high existing seroprevalence. The researchers note that these theories are not mutually exclusive, and further study is needed to better characterize the factors driving the current resurgence. In particular, it is critical to investigate the potential that emerging variants could evade antibodies developed from infection with other strains, which could inform response activities in communities around the world.  MONOCLONAL ANTIBODIES Regeneron reported interim results from clinical trials for prophylactic use of its monoclonal antibody cocktail. The trial, conducted by researchers from the National Institute of Allergy and Infectious Diseases (NIAID), included 400 participants who were determined to be at high risk for infection due to living in the same household as a COVID-19 patient. In total, 186 participants received the antibody cocktail (casirivimab and imdevimab) prophylactically as a “passive vaccination,” and 223 received a placebo. Those in the treatment group exhibited a 100% reduction in the risk of symptomatic COVID-19 disease (0 out of 186) compared to the control group (8 out of 223) and a 50% reduction in the risk of infection, including asymptomatic—10/186 (5.4%) compared to 23/223 (10.3%). Additionally, infected individuals in the placebo group had nearly 100-fold higher peak viral loads than those in the treatment group. This is a relatively small study population, but it provides evidence that there could be other options to provide protection beyond vaccines. The ability to administer monoclonal antibodies prophylactically could potentially be used to provide protection for exposed individuals who may not have time to develop immunity following a true vaccination. This study has not yet been subjected to peer review, and further study is needed to more fully characterize the prophylactic effect of the treatment. OXYGEN SHORTAGE As we have covered previously, the evolving clinical treatment standards for COVID-19 patients are driving a shortage of oxygen, in the US and countries around the world. The use of high-flow oxygen, as opposed to mechanical ventilation, is placing strain on oxygen production and use capacity, which has resulted in efforts to mitigate the increase in use and identify solutions to bolster capacity. Dr. Eric Toner, from the Johns Hopkins Center for Health Security, published an overview of the challenges, lessons from existing efforts, and recommendations to combat shortages in the coming weeks and months, based on the experiences of clinicians and public health officials in California, Minnesota, and New York (US). High-flow oxygen uses 5-10 times the volume as a mechanical ventilator, and the increased flow, and associated decrease in temperature, is causing liquid oxygen vaporizers to freeze. Some facilities are using portable oxygen canisters to mitigate this risk, which is driving a subsequent shortage in canisters and regulators. And with the overall increase in demand, the larger supply network is struggling to provide necessary deliveries to healthcare facilities. In order to mitigate these effects, hospitals and health systems are implementing a myriad of novel solutions. To reduce the risk of vaporizers freezing, some facilities are adding secondary supply lines, which can be connected to liquid oxygen tanks to divide the oxygen flow through additional vaporizers, or using warm water sprinkler systems to maintain vaporizer temperatures above freezing. The use of oxygen concentrators, as opposed to liquid oxygen tanks, can provide supplementary oxygen without the need for vaporizers. Additionally, lowering the oxygen saturation threshold for patients can reduce demand, and statewide coordination can help manage effective distribution of liquid oxygen and equipment to where it is needed most. Despite these efforts, solutions are still needed for a number of issues, including awareness of oxygen shortages and associated conservation efforts, cross-jurisdictional/interstate coordination regarding oxygen supply, transportation standards to facilitate deliveries, and manufacturing capacity for critical equipment (eg, regulators, vaporizers, cylinders).