Here we go again. The United States is now experiencing a fourth wave of COVID-19, with very rapidly rising infections. The surge in new daily cases is driven by the Delta variant, which makes up 83% of sequenced samples in the U.S. and which is estimated to be twice as transmissible as the original strain. One of the reasons that Delta spreads more easily is that a person infected with this variant has a viral load 1,000 times higher than someone infected with the original version of SARS-CoV-2.
Hospitalizations and deaths are also rising, though more slowly than cases, reflecting the fact that 49% of all Americans are fully vaccinated. Even with Delta, COVID-19 vaccines are extremely effective at preventing severe illness and death. Anthony Fauci, President Joe Biden’s chief medical advisor on COVID-19, estimates that over 99% of people dying in the U.S. from the illness are unvaccinated. But the levels of vaccination are not high enough in some areas to prevent new surges among those who are not inoculated. And with growing infections among the unvaccinated, some vaccinated people are not surprisingly getting breakthrough infections because no vaccines are 100% effective. So, what happens next? How is the pandemic likely to play out into the fall and winter? Here are six factors that are likely to drive the shape of the pandemic in the coming months.
First, local vaccination rates will continue to be the most important factor in determining what will happen
The U.S. now has a patchwork pandemic, in which communities with low vaccination rates are likeliest to see surges in infection. One recent analysis found that 463 U.S. counties now have high rates of new infection—at least 100 new cases per 100,000 residents in the past week, which is over five times the overall U.S. rate. In 80% of these counties, less than 40% of residents are fully vaccinated. The five states with the lowest rates of full vaccination—Alabama (34%), Arkansas (35%), Louisiana (36%), Mississippi (34%), and Wyoming (36%)—are all experiencing major surges.
In these five states, while 4 out of 5 people aged over 65 have had at least one shot, the vaccination rate is much lower in the 18-65 age group, and lower still in adolescents (those aged 12-17). Few adolescents in these states have had at least one dose: just 24% in Arkansas, 16% in Alabama, 17% in Louisiana, 15% in Mississippi, and 19% in Wyoming. This leaves young people highly vulnerable to the fast-spreading Delta variant. Compare these numbers with a highly vaccinated state like Vermont, where almost 100% of those aged over 65 and 68% of those aged 12-17 have had at least one dose—and cases and hospitalizations are less than 3 and 1 per 100, 000, respectively.
It is also clear that the uptake of vaccines has slowed down and in some places almost stagnated, particularly in the southern states. The U.S. went from administering more than 3 million doses a day in mid-April to only around 500,000 doses a day right now. If you live in a poorly vaccinated community—and especially if vaccination rates are stagnant or barely rising—your community is at an elevated risk of a surge. Data from this week suggest that in some states affected by surges the rate of vaccinations is increasing, but it is unclear if this trend will continue.
In highly vaccinated states, an influx of unvaccinated visitors can also create a potential set up for local outbreaks. We saw this in Provincetown, Mass., where a super-spreader event presumed to be from a large influx of unvaccinated visitors led to a major cluster (430 confirmed cases as of July 23, 2021). Of the Massachusetts residents affected in this outbreak, 69% reported that they were fully vaccinated. And it would have been much worse had the vaccination levels of the Provincetown community not been so high. But the secondary impact of these types of clusters on pockets of unvaccinated children and on high risk or immunocompromised adults will in part depend on the amount of transmission from vaccinated people who have breakthrough infections.
Moving forward, we think a few policy and social aspects will have a huge impact on whether vaccination rates increase in this country—in particular, whether there is a concerted effort to depoliticize vaccines (political affiliation appears to be driving differences in vaccination uptake) and whether more businesses and schools start to require vaccinations for participation and employment.
Second, whether public health measures are reinstated will affect how long those surges continue
In communities facing a surge related to the Delta variant, the right public health response is to restore control measures such as community-wide indoor mask mandates, social distancing rules, scaling up test and trace, and intensifying workplace and school mitigations (including improved ventilation) until vaccination rates increase. Los Angeles county, for example, recently reinstated an indoor mask mandate for everyone, regardless of vaccination status, to help curb its rapid spread of the Delta variant. Similarly, last week San Francisco Bay Area health officials urged residents of seven counties and the city of Berkeley to resume wearing masks indoors. Sound pandemic management requires tailoring measures to the local situation on the ground.
The U.S. Centers for Disease Control and Prevention (CDC) placed a significant roadblock to such tailored management when it changed its mask guidance in May, saying vaccinated people no longer need to wear masks indoors—this guidance had no nuance to account for community transmission levels or outbreak status. The guidance basically gave local governments and businesses the cover to drop mask mandates and indoor limits for both vaccinated and unvaccinated, leading both to change their behavior and putting other unvaccinated people, including children under 12, at risk. We agree with former Surgeon General Jerome Adams when he says, “the CDC urgently needs to revise its guidance to vaccinate and mask in places where cases are rising yet vaccination rates remain low.” CDC should consider releasing specific metrics for on-ramping and off-ramping public health measures that local and state public health bodies can take into consideration. Such guidance would lead to less confusion and build more public trust. Many schools are reopening in five weeks, and we think there is an urgency for the CDC to provide more specific guidance on masks, testing, and other mitigations against COVID-19 in schools. The American Academy of Pediatrics now recommends that all students over 2 years old, and all teachers and staff, wear masks, regardless of whether they have been vaccinated against COVID-19—that could help, though the need for masking should be tailored to local community transmission levels.
University and college campuses will also need to grapple with the challenges that Delta brings. A new study by Yale University researchers David Paltiel and Jason Schwartz found that colleges where over 90% of all students, faculty and staff are fully vaccinated can safely return to normalcy, but campuses below this vaccine coverage may need measures such as distancing and frequent testing of the unvaccinated.
Third, the local pattern of COVID-19 could be influenced by how much protection is provided by past infection.
Research suggests that if you have had COVID-19, you acquire some degree of immunity. In theory this might mean that if your community has low vaccination rates but a high proportion of people were previously infected, the chances of a surge from the Delta variant are lower. But we need to be careful about jumping to any conclusions. The science suggests that the immunity from past infection may be partial and short term, which is why the World Health Organization, CDC, and other public health agencies recommend that people who have been infected by SARS-CoV-2 still get vaccinated. Additionally, a new analysis from Public Health England found that reinfection is more likely with the Delta variant compared to the Alpha variant—further argument for even those who have had and recovered from COVID-19 to get vaccinated.
A fourth factor is whether vulnerable Americans will need booster shots and if some decrease in immunity will lead to seasonal increases in cases, similar to the way influenza rates rise every winter
Last week, Israel’s health ministry released data raising the possibility that the protection that the Pfizer vaccine provides against infection may wane over time. We need to be very cautious about the data: they are preliminary and based on small numbers, and other nations have not seen a similar waning. There are also supportive data based on lab studies that say that for most people, vaccine-induced immunity may last years (at least against the current variants), although such immunity may wane for those who are more advanced in age or have weakened immune systems.
After previously ruling out the need for boosters, the Biden Administration has now signaled that it is looking into recommending a booster (a third shot of either the Pfizer/BioNTech or Moderna vaccine) for people 65 and older or those with weakened immune systems. Experts are also considering whether those who received the single-shot Johnson & Johnson vaccine should get a booster shot of Pfizer/BioNTech or Moderna. At a recent senate hearing, CDC Director Rochelle Walensky said that her agency is following large cohorts of vaccinated residents in nursing homes as well as cohorts of vaccinated frontline health workers with weekly testing to understand how efficacy against vaccines may be changing over time. Such data will likely help determine whether and when boosters are needed.
Some infectious disease experts, such as the German virologist Christian Drosten, believe that COVID-19 could become a “seasonal epidemic,” with an annual rise in cases in the winter. If it turns out that immunity from the vaccine does decline over time among the elderly and immune compromised and that COVID-19 is seasonal, this combination would provide a strong case for giving these vulnerable people boosters ahead of winter.
Fifth, we don’t know exactly how common it is for vaccinated people to become infected and transmit SARS-CoV-2 to others, though so far it appears to be relatively uncommon
The good news is that all the authorized vaccines greatly reduce your chances of becoming infected (e.g. the Pfizer/BioNTech and Moderna vaccines reduce this risk by 91%)—and reduce the risk of becoming severely ill, hospitalized, or dying from COVID-19 at an even higher rate. But no vaccine is 100% effective. So we would still expect a small proportion of fully vaccinated people to get infected and sometimes transmit the virus to others.
Research is underway to try and determine just how common it is for vaccinated people to transmit SARS-CoV-2 to others and how the Delta variant impacts this risk, and the results will have a bearing on the next phase of the pandemic.
Sixth, another new variant of concern could arise
All viruses change (mutate) over time, and such mutations are more likely when a virus is circulating widely. Most mutations don’t change the ability of the virus to cause infections and disease, but some canThat means that, as long as SARS-CoV-2 is spreading, there’s a possibility that new variants of concern could arise, which could again change the trajectory of the pandemic.
The good news is that COVID-19 vaccines are highly effective against all known variants. Scientists are also confident that if a new variant arises that evades the protection of current vaccines, vaccine manufacturers will be able to quickly reformulate and test vaccines against these new variants. But currently, half of America and most parts of the rest of the world are not vaccinated; in Africa, for example, just 2% of people have received at least one dose of the vaccine. Globally, cases and deaths have gone up by 25% over the last two weeks and these continued surges are giving the virus ample opportunity to evolve. As new variants evolve, it won’t be our ability to create reformulated vaccines that will limit us. Instead, the main hurdle will be to turn those new vaccines into vaccinations here in the U.S. and worldwide.
During the 1918 influenza pandemic, one third of the world’s population was infected and society was vulnerable to consecutive waves with minimal number of tools to combat them. In 2021, we have extremely powerful vaccines in addition to tried and true non-pharmaceutical measures such as masks that can help us shape our destinies to a greater measure than was possible a century ago. But the COVID-19 pandemic has revealed that even with these tools, there are significant social and political challenges that are delaying our recovery.

A full course of two of the most widely available coronavirus vaccines is about as effective against the more contagious delta variant as it was against a previously dominant version of the virus, according to
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