Featured Journal Content

The Journal of Infectious Diseases
Accepted manuscript
The Concept of Classical Herd Immunity May Not Apply to COVID-19
David M Morens, Gregory K Folkers, Anthony S Fauci
jiac109, https://doi.org/10.1093/infdis/jiac109
Published: 31 March 2022
PDF only: https://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiac109/43207935/jiac109.pdf
[Opening Paragraphs]
There has been speculation about when in the COVID-19 pandemic we will be able to live with the virus in a manner that does not disrupt most peoples’ lives. Much of this discussion has focused on herd immunity thresholds:

A herd immunity threshold is the proportion of a population with immunity against a communicable disease agent (resulting from innate immunity, natural infection, or vaccination) above which transmission of the agent is largely prevented, except for sporadic outbreaks in under-vaccinated or otherwise incompletely protected subsets of individuals.

As commonly understood [1-7], herd immunity thresholds are reached when a sufficient proportion of the population is vaccinated or has recovered from natural infection with a pathogen such that its community circulation is reduced below the level of significant public health threat. For example, this threshold has been met with polio and measles circulation in the United States.

However, SARS-CoV-2, the virus that causes COVID-19, is so different from polio and measles that classical herd immunity may not readily apply to it. Important differences include the phenotypic stability of polio and measles viruses, and their ability to elicit long-term protective immunity, compared to SARS-CoV-2. For these and other reasons, controlling COVID-19 by increasing herd immunity may be an elusive goal…

[Closing Section]
HERD IMMUNITY AND COVID-19.
There are significant obstacles to achieving complete herd immunity with COVID-19. “Classical” herd immunity, leading to disease eradication or elimination, almost certainly is an unattainable goal. As noted, mass vaccination and aggressive public health approaches have struggled to control other (seemingly more controllable) respiratory infectious diseases, such as smallpox, measles, and rubella, all caused by viruses with limited phenotypic evolution. Controlling SARS-CoV-2 and its cycles of new variants presents a much more formidable challenge *23+. Like influenza, SARS-CoV-2 mutates continually into new variants that can escape immunity derived from infections and vaccines. It also can be transmitted asymptomatically and without pathognomonic signs, impeding public health control. SARS-CoV-2 appears not to substantially engage the systemic immune system, as do viruses such as smallpox, measles, and rubella that consistently have a pronounced viremic phase. Moreover, neither infection nor vaccination appears to induce prolonged protection against SARS-CoV-2 in many or most people. Finally, the public health community has encountered substantial resistance to efforts to control the spread of SARS-CoV-2 by vaccination, mask wearing, and other interventions.

If vaccine- or infection-induced immunity to SARS-CoV-2 indeed proves to be short-lived, or if escape mutants continue to emerge, viral spread may continue indefinitely, albeit hopefully at a low endemic level. This notably has occurred with the 1918 pandemic influenza virus, whose viral descendants still are causing seasonal outbreaks and occasional pandemics 104 years later (pandemic H2N2 in 1957, H3N2 in 1968, and H1N1 in 2009) (24), and which we have been unable, after more than 80 years of trying, to fully control with vaccines. Such factors probably make SARS-CoV-2 impossible to eradicate (only one human virus – smallpox — has ever been eradicated), difficult to eliminate over long periods within large geographic areas, and difficult to satisfactorily control even with good vaccines.

Thus, COVID-19 is likely to be with us, even if at a very low level of endemic community spread and with lower severity, for the foreseeable future. Like influenza, any level of herd protection against SARS-CoV-2 potentially can be overcome by ever-changing levels of immunity among countless sub-populations, by human movement, crowding, changes in social or prevention behaviors, by demographics, by vaccination levels, by variations in durability of infection- or vaccine-induced immunity, and by evolution of viral variants, among many other variables.

But encouragingly, after more than two years of viral circulation, and more than a year of vaccines with boosters, we now have a high degree of background population immunity to SARS-CoV-2, as well as medical countermeasures such as antiviral drugs and monoclonal antibodies to prevent progression of disease, and widely available diagnostic tests. With these interventions we can aspire to, and very likely will succeed in achieving, substantial control of community spread without the disruptions of society caused by COVID-19 over the past 2 years. We no longer need the elusive concept of “herd immunity” as an aspirational goal: COVID-19 control is already within our grasp.

Looking forward, more broadly protective vaccines could play important roles in controlling SARS-CoV-2 and its inevitable variants. Developing “universal” coronavirus vaccines (or at least universal SARS-CoV-2 vaccines that elicit durable and broadly protective immunity against multiple SARS-CoV-2 variants) is an important goal for the immediate future (23). Meanwhile, optimal COVID-19 control will require both classic, non-pharmacologic public health approaches and vaccination of many more people globally with the SARS-CoV-2-specific vaccines we already have, with booster shots and with updates to vaccine antigens if needed.

Living with COVID is best considered not as reaching a numerical threshold of immunity, but as optimizing population protection without prohibitive restrictions on our daily lives. Effective tools for prevention and control of COVID-19 (vaccines, prevention measures) are available; if utilized, the road back to normality is achievable even without achieving classical herd immunity.