Are We Hurtling or Hurdling Towards Herd Immunity for COVID-19?

Vaccines against COVID-19 were developed in record-smashing time, and now that the rollout has begun, attention is returning to herd immunity, in a real rather than hypothetical sense.

Herd immunity refers to the protection against an infectious disease that arises when a critical mass of individuals in a population becomes immune. The pathogen can’t find welcoming bodies, and the epidemic dies out. Once herd immunity is attained, mitigation measures can be relaxed. But if society opens too soon, a second and even third wave of disease can ensue – as we’ve seen.

A vaccine, engineered to evoke a strong and diverse antibody response, is more likely to build herd immunity than is natural infection.

Establishing herd immunity against COVID-19 requires that a whole bunch of ducks align. The variables include:

• vaccine hesitancy
• logistics of vaccine deployment
• efficacy
• durability (length of protection)
• sticking to the 2-shot timetable
• the ever-mutating virus

Here’s a brief description of herd immunity: history of the idea, a little necessary math, and views of experts.

Origin in Agriculture

A recent Perspective in The Lancet traces the origin of the herd immunity concept back a century to veterinarians in the US. They noted that epidemics of miscarriage among sheep and cattle didn’t go away by culling the herd, as long as new animals arrived.

“Abortion disease may be likened to a fire, which, if new fuel is not constantly added, soon dies down. Herd immunity is developed, therefore, by retaining the immune cows, raising the calves, and avoiding the introduction of foreign cattle,” veterinarian George Potter wrote in 1918.

Soon after, other investigators demonstrated herd immunity in mice and among healthy male students living in cramped dormitories at the Royal Hospital School in Greenwich, UK who contracted and passed around diphtheria.

Predicting the Percent Who Must be Immune

Calculating the percent of a population that must be immune to generate herd immunity – the herd immunity threshold – begins with the “basic reproduction number” or “R-naught” (R0). It’s the number of people to whom an infected person passes the disease, assuming that everyone is susceptible.

R0 values range from 1.3 for seasonal flu to 18 for measles. COVID-19 started out as 2 to 2.5, making it slightly more contagious than Ebola but less so than HIV, SARS, Zika, or mumps.

The more contagious a disease is, the higher the threshold. Here’s a brief calculation:

The formula 1 – (1/R0) generates herd immunity threshold.

If R0 = 2, then 1-(1/R0) = 1-1/2 = ½ = 50% of the population must be vaccinated

If R0 = 4, then 1-(1/R0) = 1-1/4 = ¾ = 75% must be vaccinated

If R0 =10, then 1-(1/R0) = 1-1/10 = 9/10 = 90% must be vaccinated

When a new variant comes on the scene that ups transmission, then R-naught increases and a greater percent of the population must be vaccinated to reach herd immunity. (Ranges are often given for different populations assessed at different times.) And so Dr. Fauci wasn’t correcting an error, wrong, or being evasive when he upped the prediction from 50 to 75% to 70 to 90% in the wake of discovery of the new variants.

It’s common sense. If more people are infected, more need to be protected to get things under control.

Marc Lipsitch, epidemiologist at the Harvard T. H. Chan School of Public Health, described the concept at a JAMA webinar December 17. “The herd immunity threshold is the point at which vaccination alone can stop transmission in the community without any other counters like shutdowns and masks. That point comes when each infection leads to less than one new infection, so the number of infections goes down.”

But herd immunity threshold is somewhat theoretical. It assumes that everyone in the projected percent of people needed to be vaccinated will be vaccinated, and that the vaccine is 100% effective – the two mRNA-based vaccines are close, but not perfect.

The best-case scenario is that everyone takes a vaccine that is 100% effective and R0 is low. If only 45% of the population wants a vaccine that works on only 70% of those who receive it, reaching herd immunity will take longer than if more people want it and/or the vaccine is more effective.

Delaying Second Shots and Countering Vaccine Hesitancy

Just like it takes at least two avocados to make decent guacamole, the clinical trials for the two mRNA-based COVID vaccines clearly showed efficacy of a two-shot protocol, with the second dose three to four weeks after the first. Delaying second shots would slow or stall reaching herd immunity, Lipsitch and Paul Biddinger, director of the Center for Disaster Medicine at Massachusetts General Hospital, said at the December webinar.

Lipsitch published a study in 2016 about the effect of lowering doses of yellow fever vaccine to stretch supplies — and the strategy dampened efficacy. “I can’t imagine it happening (for COVID) given the number of changes that would have to happen and regulatory issues,” he said.

Biddinger agreed. “I worry that the messaging is that people might not need a second dose – Pfizer suggests 50% protection with one dose. We would then have a number of partially protected people. Herd immunity needs maximal immunization efficacy. The second dose is what it takes to be fully vaccinated.”

“Why bother doing trials if we ignore the evidence? I’m concerned that it’s like panicking in football, going in all directions and what looks like it makes sense in the short term could be really creating more problems in the long run,” also agreed Peter Piot, co-discoverer of the Ebola virus and noted HIV researcher at the London School of Hygiene & Tropical Medicine, in a JAMA webinar January 28, 2021.

Another factor countering the building of herd immunity is vaccine hesitancy. Nightly news programs interview people who simply cannot be talked out of their fear. A new Commentary in Preventive Medicine looks to past epidemics to suggest that people be “incentivized” – paid – to take COVID vaccines. But it’s insulting to suggest so easily dismissing people’s legitimate fears.

Piot maintains that transparency and clear communication are vital. “Most people who hesitate have questions: how do we know within 10 months this is safe? Vaccine confidence is not just by giving more information. We have to take people’s fears seriously and listen, especially in minority communities.”

I can’t fathom how we’ll get to herd immunity by summer 2021, as some experts say, given the uncertainties and potential glitches – including ones we haven’t yet predicted or encountered.

Great Barrington Revisited – A Bad Idea

On October 4, a group of researchers from Stanford University met in Great Barrington, Massachusetts, and verbalized what some people had been thinking: why not partially relax social restrictions and let COVID-19 spread through the population, while protecting the vulnerable? That, they argued, would usher in herd immunity.

The Great Barrington Declaration was intended to help economies in the time before vaccines became available.

Objection to the Great Barrington Declaration was swift, in the form of the John Snow Memorandum, which I signed. John Snow, the “father” of epidemiology, alerted London to the source of a cholera outbreak – the Broad Street pump. One of my favorite books tells the tale, The Ghost Map, by Steven Johnson.

Many experts responded to Great Barrington by pointing out that relying on natural infection, based on the history of infectious diseases, simply wouldn’t work – and at potentially great cost.

“Herd immunity has always been a vaccination plan. It’s interesting to see people talking about giving infection to healthy young people who might do fine, and that would get us out of it,” Rochelle Walensky, MD, MPH, director of the CDC, said in a JAMA webinar October 22. Sweden tried that in March, she reminded, and it failed. “They weren’t able to protect the vulnerable, and there were lots of cases in nursing homes, with deaths per million in Sweden high, until they realized the plan wasn’t working.”

Paul Offit, a professor of vaccinology at Children’s Hospital of Philadelphia and frequent COVID commentator, agreed with Walensky at a JAMA webinar October 27.

“Herd immunity is not a natural infection plan. The premise is wrong. A virus wouldn’t just up and get itself out of business. That’s never happened for any virus. If I had to pick a perfect virus for that to happen, it would be measles. Measles induces lifelong sterilizing immunity, protection against all infections, including asymptomatic cases. That’s not going to happen for this virus. Are the 30 to 50% of the population at high risk supposed to stay indoors for years? That doesn’t make a bit of sense.”

An Endemic End?

When the Great Barrington debate raged, we didn’t yet have vaccines and the virus hadn’t yet mutated itself into forms that more readily flit from human to human. But the uncertainties – from vaccine hesitancy, to not-100% efficacy, to staying ahead of the variants, to not knowing how long protection lasts – suggest that the disease may become endemic before vaccines can usher in herd immunity. “Endemic” means the infectious disease simmers at a constant baseline level in a geographic area.

I think COVID-19 is going to fade away, perhaps in sync to natural attenuating mutations and the dampening effects of vaccines and infection. That’s what Jennie S. Lavine of Emory University and colleagues foresee in a recent report in Science.

Their model incorporates the severity of COVID-19 and the now-benign situation for the other coronaviruses. And they predict “once the endemic phase is reached and primary exposure is in childhood, CoV-2 may be no more virulent than the common cold.”

Marc Lipsitch concurs. “We don’t need zero transmission to have a decent society. We have lots of diseases transmitting all the time, some of which kill people, and we don’t shut down society. If we could vaccinate those people most at risk of severe outcomes, then this disease would be milder. If we protect 20-40% of the most vulnerable, then that’s a clearer path to getting somewhere near normal than true herd immunity.”

Piot, a 71-year-old in perfect health who was hospitalized with COVID in March and a long hauler, said, “I don’t believe we will go back to being totally normal in a few months time. We’ll probably have a gradual expansion of vaccine coverage with a few people dying, but we will need to keep some of the other measures, such as wearing masks.” (See A Virus Hunter Falls Prey to a Virus He Underestimated).

We’ll get there. To paraphrase David Crosby, it may be a long time in coming, but the darkest hour is always just before the dawn. I get my first vaccine in two days.