By Mark Thomas
Preventing catastrophic community transmission of SARS-CoV-2 is the goal of many nations. Those, such as New Zealand, that have managed to achieve prevention of wide-spread community transmission, have done so by imposing strong public health measures. These measures include:
- Strict control of all immigrants, to prevent the entry of infection into the community, with mandatory isolation of those found to be infected, and mandatory quarantine of those who may be infected but have negative test results
- Extensive testing to identify the people within the community who have become infected as the result of the occasional incursions of the virus that will inevitably occur, and mandatory isolation of infected people
- Rigorous tracing and testing of the contacts of infected people, and mandatory isolation of infected contacts, and mandatory quarantine of contacts whose tests are negative.
New Zealand, Australia, and some other nations, have shown that by implementing these measures it is possible to eliminate community transmission of SARS-CoV-2.
Most other nations have considered elimination of community transmission to be impossible or impractical. These nations have chosen instead to reduce community transmission to levels that are acceptable to their public. At present the measures that are available to limit community transmission include those described above, plus measures to reduce the mixing of people within the community, such as working from home, and closing businesses and schools, and measures to reduce the risk of transmission of infection by people with unsuspected infection, such as physical distancing, wearing masks and increased use of hand hygiene. There is no international consensus on what level of community transmission is acceptable to the public, with the result that nations have differed markedly in the recommendations from their leaders, and in the uptake of the recommendations by the public. But, as night follows day, in nations where only weak measures to limit community transmission are recommended, or where they are poorly adhered to, large outbreaks of disease have occurred.
There are only two paths that can provide an escape from the measures required either to maintain elimination, in nations such as New Zealand and Australia, or to limit the size of repeated outbreaks of infection, in nations such as the USA or the UK. Both paths depend on sufficient people in the population being immune to SARS-CoV-2 infection. It is expected that in most countries, once 60-70% of the population are immune to SARS-CoV-2 then the infection will spread only sporadically, and the number of people who become unwell will pose a manageable challenge for the health system and an acceptable burden for society. Of course, the higher the proportion of the population who are immune, the less frequent and smaller will be the outbreaks of infection that continue to occur, and the less severe the burdens on the healthcare system and society. No-one expects that widespread immunity will cause SARS-CoV-2 infection to disappear completely, but rather that widespread immunity will dramatically lessen its impact.
One path to widespread immunity is through continued spread of the infection in the community. Each person who becomes infected makes an immune response that eliminates the infection, almost always within 14 days from the onset of infection. In most people the immune-mediated elimination of infection allows recovery from illness, and also removes any risk of transmission of infection to others. These immune responses also ensure that future exposures to SARS-CoV-2 will almost always result in a brief asymptomatic infection, with almost no risk of illness in the infected person, and no risk of transmission to their contacts.
There has been considerable discussion about the tendency for people with more severe COVID-19 disease to have stronger antibody responses than people with mild disease, and also about the decline in serum antibody concentrations that commonly occurs in the weeks to months after resolution of infection. It has often been suggested that this decline in the serum antibody concentrations might lead to loss of immunity following infection and susceptibility to repeated episodes of disease. However, there is excellent evidence that infection, whether it causes mild or severe disease, almost always stimulates strong B lymphocyte memory responses (1). As a consequence, even in people whose antibody levels have declined to very low levels, within days of reinfection the memory B lymphocytes, will rapidly proliferate and synthesise very large amounts of antibody, and this rapid powerful response by the memory lymphocytes will almost always lead to second episodes of infection being eradicated before symptoms can develop.
The other path to widespread immunity is through widespread vaccination. A very large number of SARS-CoV-2 vaccines are under development. All are designed to stimulate both the synthesis of protective antibodies by B lymphocytes, and the generation of B lymphocyte memory cells. The immune responses that occur in the weeks following vaccination are essentially the same as those that occur in the weeks following natural infection. We can confidently expect that vaccination also will stimulate the proliferation of memory B lymphocytes to the same degree as occurs with infection.
A surprisingly large number of people have suggested that safe, effective SARS-CoV-2 vaccines might not be available for many years. These people also suggest that New Zealand and Australia, and other countries that have pursued elimination of infection, might instead be wise to open their borders and allow the spread of infection. These people tend not to suggest how long it would take before the spread of infection would lead to immunity in 60-70% of the population, and hence when it would be safe to discontinue efforts to limit the spread of infection.
Mathematical models suggest that two to three years of community spread would be required before 60-70% of the population had been infected. In the figure below, the red line shows the predicted number of people unwell in New Zealand with COVID-19 disease if no public health measures had been imposed (2). At the peak of disease, in July-August 2020, approximately 15% of the total population would have been unwell and the number of patients requiring hospital care would have been ten times the capacity of our hospitals. The orange “saw-tooth” line shows the number of people predicted to be unwell, in New Zealand had we intermittently imposed public health measures (shown by the vertical purple stripes), intended to mitigate rather than eliminate transmission of SARS-CoV-2. In this model the public health measures were intended to ensure that the number of patients requiring intensive care did not exceed the capacity of New Zealand’s intensive care facilities. Note that intermittent “lockdowns” would have been required until well into 2022.
Figure. The predicted proportion of the New Zealand population unwell with COVID-19 illness, between March 2020 and late 2022, in the event either of no public health interventions (red line); or of intermittent periods of public health interventions (purple stripes), intended to limit the number of people unwell with COVID-19 (orange saw-tooth line) so that New Zealand hospitals were not overwhelmed by patients requiring intensive care. (Reference 2.)
Fortunately the progress with vaccine development and testing suggests that safe effective vaccines will be available in the first half of 2021. We should anticipate that we can have the best of both worlds – long periods with no community outbreaks, interrupted by occasional clusters of infection that are quickly brought under control, followed from early 2021 onwards by a well organised community-wide vaccination programme that achieves protective immunity in a high proportion of the population. Hopefully vaccine induced immunity will last several years. If we achieve high vaccination rates there may be no need for subsequent vaccine booster doses because once border controls are removed the opportunity for SARS-CoV-2 to enter and spread in the community will lead in vaccinated people to brief asymptomatic infection that will provide natural boosting of their vaccine-induced immunity. Unfortunately unvaccinated people will remain at risk of severe disease. High levels of vaccination may be expected to provide our communities with the best possible protection against COVID-19.
Gaebler C, et al Evolution of antibody immunity to SARS-CoV-2. bioRxiv November 5 2020. doi: https://doi.org/10.1101/2020.11.03.367391
James A, Hendy SC, Plank MJ, Steyn N. Suppression and mitigation strategies for control of COVID-19 in New Zealand. At: https://www.tepunahamatatini.ac.nz/2020/03/26/suppression-and-mitigation-strategies-for-control-of-covid-19-in-new-zealand/
Mark Thomas is an Associate Professor in Molecular Medicine and Pathology at the University of Auckland. He is an expert in infectious diseases.