An mRNA Vaccine against SARS-CoV-2 — Preliminary Report from NEJM

https://www.nejm.org/doi/full/10.1056/NEJMoa2022483

BACKGROUND

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.

METHODS

We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group.

RESULTS

After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti–S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively).

After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.

CONCLUSIONS

The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461. opens in new tab).

 

SARS CoV-2 Vaccine Update 

The most talented scientists around the world are busy developing vaccines for the virus that causes COVID-19. There have been some encouraging developments in recent weeks. There are 18 vaccine candidates under clinical evaluation world wide right  now.  The one that’s the furthest along is an 8,000 person Phase III trial in the UK.

There aren’t any Phase III trials underway in the US yet, but Moderna vaccine expects to go to Phase III at the end of the month or the beginning of August. Moderna’s vaccine had positive early results, developing antibodies against the virus. Another Covid-19 vaccine candidate being developed by Pfizer and a  German company called BioNTech had positive data in early tests.  Their preliminary findings last week (in this pre-print) developed antibodies and the vaccine was well tolerated.  The company said it remains on track to be able to deliver approximately 500 million doses per year, and possibly up to one billion doses per year, beginning in 2021 from both its internal U.S. manufacturing site and a strategic collaboration with Lonza.

Inovio has stated that they have promising early data (Phase I). In that Phase I trial 94% of people developed a specific immune response in six weeks after receiving two doses of the vaccine INO-4800 and by eight weeks, the vaccine regimen was found to be safe and well-tolerated with no serious reactions.

Under-served Areas Promised Some Testing Relief

There have several areas of the state that have had a dearth of COVID testing opportunities because community testing has been lacking or absent.  Examples tend to be in areas with lower average incomes like in Maryvale and South Phoenix. Looks like those areas will be getting some relief. 

Last week the ASU Biodesign Institute and the ADHS sealed an agreement which will provide free saliva diagnostic testing in high-need under-served communities around the state. The testing began yesterday in the West Valley. The tests are by appointment only, which can be scheduled by visiting azhealth.gov/testing

ADHS will be paying ASU up to $12M to fund the initiative. They’ll be using the new test procedure developed by ASU’s Biodesign Institute a few months ago. It’s the first saliva-based test in the state.  They’ve been using it over the past several weeks to test critical workforce including healthcare workers, first responders, and infrastructure personnel. ASU is also using the saliva-based test with employees and students.

ASU’s turn around time is less than 2 days- so that’s an added bonus for these communities!

Undocumented immigrants’ lack of access to COVID-19 testing threatens all of us

We published the above opinion piece in the Arizona Republic this week that urges public policy changes to improve access to testing and treatment of undocumented persons. Congress has left millions of immigrants, many of them essential workers, without access to necessary COVID-19 care, threatening all of our health.  

You can read our opinion piece in the July 8 Arizona Republic

Dr. Gerald’s Arizona COVID Trend Update

Dr. Gerald updated his analysis of COVID epidemiology and hospital admission/capacity trends over the weekend. Here’s a link to the 6-page analysis. Below are a few of the take-aways:

Given the reporting lag, it is unclear how PCR testing capacity changed this past week; however, the percent of patients testing positive continues to increase from a low of 4.9% in mid-May to a new high of 23.4% this past week

From a May 22 plateau, total Covid-19 hospitalization has increased 301% from 1093 to 4384 occupied beds. Increases in general ward occupancy have outpaced ICU occupancy, 345% versus 191%, respectively. Continued increases in new cases are expected to drive additional hospitalizations for the near future.

899 (52%) of Arizona’s 1730 ICU beds were occupied for Covid-19 care, a 13% increase from last week. An additional 174 (10%) beds remain available which is about the same as the 171 beds available last week. About 50 ICU beds were added to Arizona’s total capacity on July 10th.

Most ICUs are at or over their capacity limits with regard to an adequate supply of health care workers; some hospitals are near or at capacity for ICU beds. Widespread personnel shortages are already being reported in critical care settings. Local conditions will provide a better indicator of critical capacity than state-wide trends.

With 204 deaths reported to date, the week ending June 28th is now the week with the largest number of Covid-19 deaths eclipsing the 202 deaths the week ending June 21st. This increase is consistent with the recent increases in new cases. Given that case counts are still increasing, a larger number of deaths in the coming weeks is expected.

The shift towards younger, working-age adults has abated; therefore, future case increases will be more directly tied to hospital utilization and deaths.

June typically marks the nadir of Arizona hospital admission Arizona. From now until January, non-Covid hospitalizations are expected to increase putting additional strain on hospital capacity.

Goal Finally Set to Improve AZ COVID Test Turn-Around Times

For the last several weeks our public health response system has been impaired because of the slow turn around times for the diagnostic PCR tests. Much of the public discourse has focused on the shortage of testing that’s available but there’s been less discussion of the poor turn-around times (between 6-8 days and often more).

Slow turn-around times impair the public health response because folks that get tested don’t know their status for several days.  When they don’t know their status- it’s less likely that they’ll make the behavioral changes needed to prevent the spread of the virus (e.g. they’re unlikely to isolate). 

Also, contact tracing effectiveness is nullified because the folks at the county health departments get the case report several days too late. By the time they’re able to do the case investigation the person is likely no longer infectious- and the opportunity to intervene has passed. Contacts may already be symptomatic and in some cases may have even recovered.

Those are reasons why we really need to improve turn-around times.

We got word this week that there is now a goal to improve those turn around times. The ADHS has publicly committed to increasing diagnostic capacity to 35,000 units per day by the end of July. To accomplish that, they’ve earmarked $2M to Sonora Quest to buy instruments/reagents etc.

Hopefully they’ll also be looking at: 1) the specimen courier services; 2) the instruments needed for the analysis; 3) staffing to make it happen; and 4) report out logistics.

We also need a new metric in the ADHS dashboard that tracks  turn-around time. Public metrics are essential to accountability and performance improvement. Without a public metric I’m afraid that this super-important performance measure won’t be a priority for leadership.

AZ Legislative Session Summary: One for the Ages

The 2020 regular session will stand out as one of the most unpredictable, unforgettable years ever. Session lasted 135 days but was suspended for more than 40% of that time because of the pandemic.  The year began with loud, crowded committee meetings and ended with near-empty buildings and remote voting.

Legislators introduced 1,734 bills this year (more than any session on record) but had the fewest number of bills signed into law in recorded history.  Only 5% of those bills made it to the Governor’s desk. Nearly 90% were bipartisan.

Just before the session was suspended, they approved a “baseline” budget which was basically a continuation of last year’s spending, adjusted to pay for projected growth in health care and education enrollment. It also included an additional $105M to address the COVID-19 pandemic.

Here are some of the bills that passed:

  • A bill requiring AHCCCS to ask for federal authorization to reimburse the Indian Health Services and tribal facilities to cover the costs of adult dental care.

  • A bill that increases federal funding for hospitals that provide care for AHCCCS patients by requiring the facilities to contribute the matching funds needed to bring more federal dollars to Arizona.

  • Increasing suicide prevention training for school counselors and social workers, and by providing more information about mental health resources to students and mandating all public and charter schools include information on school ID’s (grades 9-12) like the phone number for a national and local suicide prevention hotline and the number for a network of local crisis centers. 

  • A Mental health parity bill that expands access to mental health resources and creates committees responsible for identifying new ways to ensure students and other Arizonans have access to mental health care.

Most of our policy priorities were not achieved. Bills to provide dental services for pregnant women enrolled in Medicaid and encouraging women to complete post-partum visits didn’t pass.

We were also unable to get bills through that would classify electronic cigarettes as tobacco products so they would be covered by the Smoke Free Arizona Act. We also weren’t able to get a Tobacco 21 passed this year either. 

A bill that would have decriminalized evidence-based syringe service programs also didn’t make it. Likewise, no progress was made to improve access to care through additional graduate medical education enhancements nor the state loan repayment program.

There had been support for some limited criminal justice reform but the bills that would have improved sentencing standards including second chances didn’t pass in the end. Bills that would have made it harder for law enforcement to take a suspect’s assets, and require state agencies to give most occupational licenses to individuals who have been convicted of a drug offenses also didn’t get over the line.

As a refresher, here was our set of 2020 Legislative Session Priorities (ppt).

Journal Articles of the Week

Visualizing the effectiveness of face masks in obstructing respiratory jets 

Physics of Fluids 32, 061708 (2020)

Abstract:

We use qualitative visualizations of emulated coughs and sneezes to examine how material- and design-choices impact the extent to which droplet-laden respiratory jets are blocked.

Loosely folded face masks and bandana-style coverings provide minimal stopping-capability. Well-fitted homemade masks with multiple layers of quilting fabric and cone style masks were the most effective in reducing droplet dispersal.

_________

Testing for SARS-CoV-2 Infection Among Incarcerated and Detained Persons

A new MMWR report details an investigation conducted by CDC and the Louisiana Department of Health to determine SARS-CoV-2 infection prevalence in quarantined dormitories in a Louisiana correctional facility. 

Fulbright Public Policy Fellowship Applications Being Accepted

Applications are now open for the Fulbright Public Policy Fellowship. The program provides opportunities for U.S. early and mid-career professionals and practitioners to serve in placements in a foreign government ministry or institutions around the world.

The program includes an independent research component focusing  on an issue related to the Fellow’s in-country work. Successful candidates will include early to mid-career entrepreneurial and self-starter professionals with a graduate degree in a public-policy related field (e.g., JD, MPA, MPH) and a minimum of three to five years of full-time work experience.

Postdoctoral candidates and practitioners active in the academic, public, or private sectors with a record of experience and accomplishment in a public policy related area are encouraged to apply.

Executive Orders Close Bars, Gyms, Delays the Start of School

In a series of 5 new executive orders, the governor has limited gatherings of people both indoors and outdoors to no more than 50 people, and has ordered a 30-day shutdown of bars, gyms, movie theaters, water parks and tubing. Another order delays the school start date until August 17, which he described as an “aspirational date”.

Gatherings of more that 50 people are allowed if a local government jurisdiction authorizes it and certifies that the even will have adequate mitigation measures. 

The closing of bars is limited to places that hold a series 6 or 7 liquor license. A typical restaurant would hold a series 12 license and can therefore remain open. 

However, series 6 or 7 license owners that get more than 1/2 of their revenue from food sales can remain open with dine-in or drink-in service.  I’m not sure where the data is that documents whether a place gets more than half their revenue from food- hopefully there is a clear data set to make that determination- otherwise that’ll become a big loophole.

When the 30 day closure ends they must adhere to public health regulations, post them for the public.  Cities and counties will be responsible for enforcement.

Compliance is king when it comes to public health interventions. Let’s see what compliance looks like before drawing any conclusions about the effectiveness of these interventons.

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