Author: Will Humble

A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2

DOI: 10.1126/science.abc6810

Population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates.

We estimate that if R0 = 2.5 in an age-structured community with mixing rates fitted to social activity then the disease-induced herd immunity level can be around 43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population.

Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity, rather than an exact value or even a best estimate.

The ADHS is implementing a new Surge Staffing Initiative. Similar to the Surge Line, this program will try to stabilize community hospital hot spots to deal with the ongoing surge of patients. It may also provide some relief for nursing staff. 

The initiative allows hospitals to apply to receive out-of-state nurses. The nurses will be deployed for a 6 week period for up to 20% of their licensed capacity at no cost.  The Arizona Surge Line staff will make the deployment decisions. 

Hospitals received the application forms this week. Here’s an example of the application questions and attestations.  

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).

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.

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!

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 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.

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.