We've learned a vast amount about SARS-CoV-2 in the past year. We know it comes from bats, most likely from Yunnan, China (asamonitor.pub/3rVUMXJ). We know that variants are emerging that increase infectiousness and escape humoral immunity (Science 2020;370:1464-8; Nature March 2021). We can track coronavirus evolution in infected individuals and know that this evolution is greatly enhanced in immunocompromised individuals (asamonitor.pub/3eN75lG; N Engl J Med 2020;383:2291-3; Nature February 2021). We also know that coronavirus reinfections occur, as has been documented for the four endemic coronaviruses, because of waning humoral immunity (MMWR 2021;70:273-7; Nature Medicine 2020;26:1691-3; Nature Communications 2021;12:63). We know that our vaccines work incredibly well, but that the vaccines are less effective against emerging variants (asamonitor.pub/3lv0ptF; Nature February 2021). Science has hit the ball out of the park with this explosion of knowledge and the unprecedented development of three FDA Emergency Use Authorization-approved vaccines in fewer than 12 months.

What now? Is it over? Will the vaccines protect us? Can we visit friends and family? Can we visit our aging parents and grandparents or take that trip to Greece? Or Brazil? Is it safe to take a cruise to Antarctica to see the solar eclipse on December 4, 2021?

No!

At the time of this writing (March 16th), 9% of the U.S. population has been infected with the coronavirus and 20% has been vaccinated per the CDC. Based on the CDC guidelines that everyone should be vaccinated, we can calculate that 27% of the U.S. population is immune.

Herd immunity is a concept introduced to describe how vaccinating most of a population helps protect everyone. When most individuals are vaccinated, often defined as >75% of the population, then the unlucky person who becomes infected typically doesn't pass the infection to someone else, because nearly everyone else is immune. The actual threshold for herd immunity varies with the contagion and behavioral response and may be as low as 40%-60% in some settings (Science 2020;369:846-9).

Israel has launched the most aggressive vaccination campaign in the world. As of this writing, 11% of Israelis have had COVID-19, 71% have been vaccinated, and thus 75% are immune. The results are dramatic. Daily case rates in Israel have decelerated 32% since January, and daily death rates have decelerated 34% since January. Even with that dramatic progress, Israel still ranks #9 globally for the most cases per capita last week (early March) and #27 globally for the most deaths per capita last week (early March).

We know from Israel that we will not reach herd immunity in the U.S. until we have at least tripled the number of individuals vaccinated. We also know that even after reaching 75% immunity, there will still be unacceptably high levels of illness and death from COVID-19, just as Israel is still experiencing.

“Science has hit the ball out of the park with this explosion of knowledge and the unprecedented development of three FDA Emergency Use Authorization-approved vaccines in fewer than 12 months.”

President Biden has announced that we should have enough doses to vaccinate every American by the end of May 2021. If we allow another two months to inject all available doses, then we may have nearly the entire population vaccinated by the end of July. If everything works as hoped, by then we will reach herd immunity by the end of summer. Within our borders, and within communities that have embraced vaccination, it will be “over.”

Outside our borders, and within communities that have resisted vaccination, the pandemic will continue to rage.

There are two main challenges between here (mid-March) and there (late July). First, the more infectious B.1.1.7 variant is now circulating in the U.S. This variant drove the January surge in Israel and is currently driving the surge in Europe (asamonitor.pub/38ONy0b). It has been reported in all 50 states and is now growing exponentially in the U.S., even as daily cases have gradually declined (asamonitor.pub/3vtlHN3). Second, in the mistaken belief that the worst is behind us, many states and local jurisdictions are rolling back non-pharmaceutical interventions such as mask wearing, social distancing, and avoiding indoor crowds. As Dr. Anthony Fauci stated on “Meet the Press” two days ago, “When I hear pulling back completely on public health measures, saying no more masks, no nothing like that, that is risky business.... Don't spike the ball on the five-yard line. Wait until you get into the end zone. We are not in the end zone yet (asamonitor.pub/3bRyOzx).”

Yes!

The Pfizer-BioNTech mRNA vaccine demonstrated a startling 95% efficacy without any serious safety concerns in the phase 2/3 study (N Engl J Med 2020;383:2603-15). Similarly, the Moderna vaccine demonstrated 94% efficacy in the phase 2/3 study without serious safety concerns (N Engl J Med 2021:384:403-16).

Interim results from the phase 3 ENSEMBLE study (NCT04505722) evaluating the safety and efficacy of the Janssen vaccine looked at efficacy across three distinct geographic regions: the U.S., South Africa, and South America (Argentina, Brazil, Chile, Colombia, Mexico, and Peru). Brazil and South Africa were notable for the widespread distribution of coronavirus infections with the E484K “escape” mutation. In the U.S., the vaccine was 72% effective, while vaccine efficacy in South America and South Africa were 66% and 57%, respectively.

Israel's largest health care organization recently published its outcome data with the Pfizer-BioNTech mRNA vaccine (New Engl J Med February 2021). Approximately 600,000 vaccinated individuals were matched in a 1:1 ratio with appropriate clinical and demographic criteria. In the 14-20 days following the first vaccination, new infections were reduced 46%, hospitalizations were reduced 74%, and severe disease was reduced 62%. In the seven days following the second dose, new infections were reduced 92%, hospitalizations were reduced 87%, and severe disease was reduced 92%. Toward the end of the study period (12/20/2020 to 2/1/2021), up to 80% of the COVID-19 cases were of the B.1.1.7 variant. The documented efficacy against the B.1.1.7 variant is encouraging.

Although humoral immunity wanes, T cell response to infection and vaccination apparently remain robust for many months, or even years, even against the known variants (Nature Immunology March 2021; asamonitor.pub/3bRJRJe). The vaccines work. Get vaccinated.

Maybe

The CDC has issued guidelines for fully vaccinated individuals (asamonitor.pub/30PzNdh). Quoting from the guidelines:

“Fully vaccinated people can:

  • Visit with other fully vaccinated people indoors without wearing masks or physical distancing

  • Visit with unvaccinated people from a single household who are at low risk for severe COVID-19 disease indoors without wearing masks or physical distancing

  • Refrain from quarantine and testing following a known exposure if asymptomatic”

Thus, if your friends and family are all vaccinated, you can visit indoors without issue. If some are not vaccinated, then visit with members of a single household (e.g., a “pod”) to avoid the risk of cross-pod transmission.

Maybe

One major concern about visiting elderly family members is the possibility that even though you are vaccinated, it is possible that you might still be a carrier and transmit the coronavirus. There is now good evidence that vaccination not only prevents symptomatic infection, but also prevents asymptomatic infection (Authorea February 2021). Asymptomatic infection is the same thing as a silent carrier. Thus, once vaccinated, it is very unlikely that you will be a carrier and can transmit the disease to anyone.

Be Careful

Starting in May, Greece will welcome vaccinated tourists (asamonitor.pub/38Kj1Re). This could be your chance to visit Greece without hordes of Europeans crowding your views and driving up the cost of your Mediterranean resort. Sounds great, yes?

Things could go very wrong. Currently only 8% of Greeks are vaccinated, and just 10% of the population appears to be immune. Cases and deaths are rising in Greece, just as they are throughout continental Europe. You might arrive and be caught in a new surge of cases. The European Union is lagging well behind the U.S and the U.K. in vaccination.

More generally, the anticipated success of vaccination in the U.S. will create a grim scenario over the next few years as life returns to normal here while the pandemic rages elsewhere. Much of the world may not see herd immunity through vaccination until late next year or 2023. This will affect international travel, introducing unique risks to local infrastructure and health care.

Perhaps your next vacation should be to Yellowstone National Park, not Athens.

Bad Idea!

Brazil is one of the countries whose government has actively spread false information about COVID-19. The results have been horrific, and viral evolution is taking very unwelcome turns in Brazil. After apparently reaching herd immunity through infection alone in Manaus, Brazil (at a terrible cost in lives lost), cases surged again in December and January (Science 2021;371:288-92; Lancet 2021;397:452-5). As noted by Sabino et al., there are four explanations: 1) the earlier estimate of 76% infection could be an overestimate, 2) immunity may have begun to wane by December, 3) the B.1.1.7 and P.1 variants may be causing re-infection, and 4) the B.1.1.7 variants and the P.1 variant may have raised the herd immunity threshold because of increased infectiousness.

Brazil does not report vaccination data, but the Bolsonaro government has been openly hostile to vaccination (asamonitor.pub/3llSXRF). Brazil seems to be running its own experiment in coronavirus evolution, along with promoting disproven and discredited therapies, and generally mismanaging the pandemic. I don't recommend signing up for this experiment.

Probably

My wife, Pamela, and I (SS) have signed up for a cruise to visit Antarctica at the end of this year to see a total solar eclipse (asamonitor.pub/3vwHjba). I had never imagined visiting Antarctica or even the possibility of seeing a total solar eclipse there. However, after learning of this eclipse, it immediately bubbled to the top of my bucket list. If you haven't seen a total eclipse, it is truly one of nature's wonders.

Full vaccination is a requirement for both the travelers and the ship's crew. If you are vaccinated, then we invite you to join us!

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1-(1-fraction vaccinated)∗(1-fraction infected)

SLS: Daily COVID-19 Update. Data from JHU and OurWorldInData.org. Subscribe at https://groups.google.com/u/1/a/slshafer.com/g/steves-covid-19-updates.