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Disease forecasting, especially with an emerging new pathogen, is always fraught with uncertainty. But there are signs that the Delta variant’s summer tear through the unvaccinated American South is the first phase of a protracted and scary new chapter in the coronavirus pandemic.

It is one that could eventually consume most of the nation.

This latest fourth wave began, among other places, in southern Missouri in June, before spreading quickly across conservative southern states where vaccinations among those under the age of 65 are almost 40 percentage points lower than in the Northeast. Among those aged 12-17, the gap is even greater.

Now, some 100,000 Americans are hospitalized with COVID-19, a number almost as high as during January’s COVID-19 peak, and we are at over 1,500 deaths per day and climbing. Even worse: The spike continues to spread both north, consuming the Midwestern states of Indiana, Illinois, and Ohio; and west into Texas, Oklahoma, and Kansas. At least one other new front of COVID-19 surge has also begun following the Sturgis Rally in South Dakota, and is now at risk of entering adjacent areas.

The comparison to the situation in the United Kingdom was, at least a few weeks ago, encouraging. There, a massive Delta wave gave way to a sudden decline in cases, even as the country opened up again. Their reported cases rose from roughly 2,000 per day to over 40,000 by the last week of July, then came down in August to almost half that level.

But now the numbers are back up to over 30,000 cases per day. At this point, there is no end game for the U.K. epidemic, and that is grim news for the United States, which pales in comparison when it comes to vaccine uptake.

So a big unknown for the U.S. is whether a very modest slowing of this latest Delta surge over the last few days could continue, or whether it picks up steam like it did in the U.K. Given the vast pool of the unvaccinated across the midsection of the country, I think we’re heading for trouble.

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For the U.S., the latest University of Washington-Institute of Health Metrics and Evaluation (IHME) projections forecast that by the fall, we could hit over 2,400 deaths per day, and reach between 700,000 and 800,000 Americans dead by Dec. 1. In so doing, we will have exceeded the estimated number of Americans who died from the Spanish flu.

Reaching these grim milestones will have a profound and adverse impact on the health and security of the nation. There are two major attendant concerns, and while they echo problems since the pandemic began well over a year ago, they are specific to this moment.

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Since the beginning, we have seen how hospitals and ICUs can struggle when overwhelmed with a surge of COVID-19 patients, which in turn is increasingly impacting everyone else—even vaccinated people who are not infected, but need other care. Such findings are confirmed by a recent NIH study.

But in this latest phase, it’s not only an influx of patients but also the accumulating losses of trained health professionals that is so worrisome. Burnout has been a problem throughout the pandemic. Yet overwhelmed nurses and other hospital staff are leaving the profession and their posts due to a combination of factors that include exhaustion and the demoralization of taking care of so many dying young and middle-aged patients who refused vaccines. As The New York Times reported this past week, there were some 2,000 fewer nurses working in the state of Mississippi—currently deep in the throes of a COVID-19 explosion—than there were as recently as Jan. 1 of this year.

There is increasing reliance on traveling nurses, but as COVID-19 accelerates nationally, this resource might soon be depleted. Some hospital systems across the South are already on the verge of collapse due to the flood of COVID-19 patients, staffing shortages, and ambulance diversions. Patients with non-COVID-related illnesses and conditions such as heart attacks, strokes, and trauma are paying the price of unavailable hospital beds and emergency rooms.

Meanwhile, business leaders and the Biden administration have appropriately begun employer and federal vaccination mandates, respectively. These are necessary steps to ensure society can continue to function during this terrible time in the pandemic. In order to remain in the workforce or because they see their friends or family fall ill, we might anticipate that there will be some “auto correction” as some Americans finally agree to be vaccinated.

But ultimately, some unknown percentage of those 80 million still unvaccinated will dig in and continue refusing vaccinations, even if they have to risk unemployment and other penalties. Some surveys indicate that the defiance is deep-seated, so we should expect a sizable number of marginalized, unvaccinated, unemployed, and profoundly angry Americans. These are the groups who might gravitate to leading or taking part in political violence, as we got a taste of with anti-lockdown protests last year.

This fall, we could enter a period of great instability, and possibly one that resembles the unrest linked to Civil Rights and Vietnam War protests during the late 1960s. The differences between now and previous waves or surges of the pandemic include some signs of acceleration in pandemic aggression arising from an increasingly disenfranchised far right, an even more exhausted and depleted health system, and in some cases, the lapse of federal aid measures like eviction protection and federally boosted unemployment.

The Biden administration should look to potential homeland-security mitigation strategies. They include emergency training for a fresh health-care workforce while accelerating emergency recruitments to help fill the gaps for nursing and other staff shortages. In addition, we still—in September 2021—need a comprehensive plan to vaccinate the nation. While the Biden administration boasted last month that 170 million Americans were fully vaccinated, the irony of course is this is exactly why we are under threat. At least 80 million eligible Americans were also fully unvaccinated. Two recent surveys found that the demographics of unvaccinated Americans are dominated by white Republicans or those who voted for Trump in the 2020 election.

The high infectivity—or “reproductive number”—of the Delta variant means that close to 90 percent of the U.S. population (roughly 290 million people) will need to be fully vaccinated. Based on breakthrough rates even among highly vaccinated populations in Israel, it is increasingly likely that three mRNA (Pfizer BioNTech or Moderna) immunizations or two adenovirus (Johnson & Johnson) immunizations may be required to keep most people safe. Preliminary evidence from Israel suggests that such boosters may restore or correct the waning immunity seen after two mRNA immunizations, but this requires confirmation and review by the FDA and CDC, which are still rolling out their own programs.

Reaching such benchmarks will be daunting and require a comprehensive strategy of “vaccine diplomacy” to reach out to conservative groups and leaders, together with a global plan to vaccinate the world. We’ll also need FDA approvals or at least authorizations for all school-aged children, not just those over the age of 12. For this, we should also look to protein-based vaccines, such as the as yet unapproved Novavax or the vaccine my colleagues and I are developing at the Texas Children’s Hospital for parents who might be more accepting of this older and more familiar technology.

Other steps required include maximizing employer mandates and those for federal agencies, and, as I have been working to do for months, being more aggressive in combating disinformation. We should consider potential sanctions against members of the U.S. Congress who deliberately promote dangerous health practices, to take just one example.

Even these measures may not get us to the last mile. It’s hard to estimate the number of last holdouts who are deeply suspicious and resentful of vaccinations, but we must recognize that this group will likely become the ones responsible for both continuing this current surge and even the potential evolution of new virus variants, and that some might even act on their anger and resentment. While we need a more assertive White House making the case to the American people that full and complete vaccinations are essential to our safety, we also need to brace for an even uglier wave of pandemic backlash.

Read more at The Daily Beast.

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