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dcyphr | Herd Immunity: Understanding COVID-19

Basic Concepts of Herd Immunity

Acquired immunity is achieved when an individual is infected with a pathogen or is vaccinated, and their immune responses “learn” a response against that pathogen. Herd immunity is essentially the acquired immunity of the population. It refers to the protection of susceptible individuals (i.e., children and the immunocompromised), with no acquired immunity when a sufficiently large proportion of immune individuals exist in the population. The goal of vaccination is to produce herd immunity.

The amount of people immune to a pathogen impacts disease transmission. This is because transmission stops with people who are immune, and they cannot transmit the pathogen to other people. If there are too few susceptible people in a population, the pathogen cannot successfully spread and its prevalence will decrease. The point at which the number of susceptible people falls below the number of susceptible people necessary for transmission is called the herd immunity threshold. Above this threshold, herd immunity begins to take effect and susceptible people are protected from infection.

Important parameters for herd immunity are R0, the basic reproduction number, and Re, the effective reproduction number. Re is the average number of infections a single infected person can generate in a population with both susceptible and non-susceptible populations. R0 differs from Re in that it only deals with a completely susceptible population. The larger the R0, the more transmissible the pathogen, so a larger proportion of the population must be immune. Re changes dynamically as an outbreak unfolds and more people are infected and gained acquired immunity. The goal of vaccination programs is to bring the value of Re below 1, where the pathogen will not continue to spread, and its prevalence in the population declines. 

Establishing Herd Immunity within Populations

In real-world situations, assumptions of equal population density and that all infected individuals acquire complete immunity are not met. The magnitude of protection by herd immunity depends on variations of these assumptions.

R0 depends on the pathogen and the population in which it is transmitted. A single pathogen will have different R0 values based on the characteristics of a population experiencing an outbreak. These characteristics include population density and structure, differences in contact rates across demographic groups, among others. This means different populations have different herd-immunity thresholds. 

To establish herd immunity in a population, vaccination must prevent onward transmission, not just disease. For example, with SARS-CoV-2, asymptomatic hosts can be highly infectious even though they don’t have clinically diagnosable COVID-19. Even after herd immunity is established, the efficacy of herd immunity depends on the strength and duration of the acquired immunity. For pathogens such as measles, lifelong immunity is generated, such that herd immunity is highly effective. This is rare. For many other infectious diseases, immunity wanes over time, such that herd immunity is less effective and outbreaks can still occur.

Herd Immunity and SARS-CoV-2

The SARS-CoV-2 pandemic has caused over 3.5 million clinically confirmed cases and over 250,000 deaths worldwide. Trials to evaluate vaccines and therapeutics are ongoing. However, it is unknown whether these trials will produce effective interventions.

Various studies have estimated R0 for SARS-CoV-2 to fall in the range of 2-6. This wide range reflects the difficulty of estimating R0 during a pandemic. These values most likely do not indicate a complete picture of transmission in all countries.

Assuming an R0 estimate of 3 for SARS-CoV-2, the herd immunity threshold is approximately 67%. This means that the incidence of infection will decline once 67% of the population acquires immunity to SARS-CoV-2. Again, this model relies on simple assumptions. But, it can give us a basic idea of the number of individuals that would be needed to be infected in the absence of a vaccine to achieve herd immunity naturally.

Consequences of Reaching the SARS-CoV-2 Herd Immunity Threshold in the Absence of a Vaccine

An important measure to evaluate the impact of SARS-CoV-2 spread is the case fatality rate (CFR). CFR is the proportion of deaths attributed to a certain disease among all cases of that disease. There is significant uncertainty in the CFR for COVID-19, and it is also sensitive to the age structure and distribution of comorbidities in a population. Current estimates of CFR point to 1.38%.

A more relevant measure to evaluate the impact of SARS-CoV-2 spread is infection fatality rate (IFR). IFR is the proportion of deaths caused by a disease among all infected individuals. IFR differs from CFR in that it attempts to account for asymptomatic and undiagnosed infections. IFR is always lower than CFR because some cases will not be reported. The number of deaths resulting from combining IFR with meeting the herd immunity threshold can be calculated with caution, assuming an unchanging IFR across countries and does not consider factors such as access to healthcare that change IFR. The worldwide number of deaths is estimated to exceed 30 million people worldwide if herd immunity is to be naturally achieved. 

In reality, CFRs and IFRs vary dramatically across different countries. Factors that contribute to this variability include testing biases, age demographics, and strain on healthcare systems. Especially important is the strain on healthcare systems, as achieving herd immunity in the absence of a vaccine requires a large proportion of the population to become infected. Depletions in healthcare resources lead to both elevated COVID-19 mortality and overall mortality. These depletions would be especially devastating for countries with limited public health infrastructure and in vulnerable communities such as prison and homeless populations.

Epidemiological Considerations for SARS-CoV-2 Herd Immunity

The above analysis is limited since the transmission and infection dynamics of SARS-CoV-2 are not well-characterized. Complexities in viral spread and infectivity, variations in R0, variable infection rates in different demographic groups, among others are important epidemiological factors in herd immunity. However, they are difficult to estimate given the limited data available.

The assumption of a uniform R0 is unrealistic. R0 is also complicated by superspreading events when favorable circumstances for high rates of transmission arise.

Factors that influence individual susceptibility, pathology, and disease outcome are not well-understood. Further studies are necessary to understand determinants of COVID-19 susceptibility and severity.

Immunological Considerations for SARS-CoV-2 Herd Immunity

The ability to establish herd immunity against SARS-CoV-2 is based on the assumption that infection generates sufficient, protective immunity. Currently, it is unclear whether humans are able to generate sterilizing immunity to SARS-CoV-2. While there are promising findings, it is important to consider whether antibodies generated against the virus wane over time and how long acquired immunity will last. Previous studies of other coronaviruses showed that antibodies decreased after 1-2 years after infection. If this is also true for SARS-CoV-2, herd immunity may not be achieved in the absence of recurring vaccination.

Recap

Herd immunity provides protection to susceptible individuals by minimizing transmission between a susceptible individual and an infected person. In its simplest form, herd immunity will begin to take effect when a population reaches the herd immunity threshold (proportion of immune individuals crosses 1-1/R0). However, in real-world populations, the situation is much more complex. Epidemiological and immunological factors, such as population structure, variations in transmissibility, and waning immunity lead to variation in herd immunity and herd immunity threshold for different populations. These factors need to be taken into account when discussing herd immunity in populations. There are two approaches to build herd immunity against SARS-CoV-2: (1), a mass vaccination campaign, or (2) natural immunization by infection. However, the consequences of (2) are severe. A large fraction of the global population would need to become infected, causing millions of deaths. In the absence of a vaccination program, establishing herd immunity should not be the ultimate goal. Instead, policies that protect vulnerable groups should be enacted in hopes that herd immunity will be achieved as a byproduct of such policies.