Last updated by The POOG on February 05, 2021.
As more experience with the disease is had and more research is done, two question arise. Firstly, is lasting immunity conferred on recovered patients? Secondly, if not permanent, how long may it last and at what strength?
These are critical questions for vaccine development and epidemic management.
Key Points of the Immune System
The issue with any viral infection is the antibody response of the immune system and its persistence. The response differences among virus families and individual viruses. Here we are concerned with the corona virus, SARS-CoV-2, which is the virus of the COVID-19 pandemic.
A 1990 study of a common cold corona virus induced in 15 volunteers by Callow et al., found that
antibody concentrations started to increase 1 week after inoculation and reached a maximum about 1 week later. Thereafter antibody titres slowly declined. Although concentrations were still slightly raised 1 year later, this did not always prevent reinfection …
This compares with a study of the SARS-CoV-2 virus by Long, Liu, et al. of 26 patients that found that virus detection (seroconversion) was found as early as 4 days after symptoms and reached a plateau about day 15. The population was slowly declining up to the point the study stopped around 25 days.
Long, Tang, et al. studied a group of 37 asymptomatic individuals in the Wanzhou District of China along with 37 sex-, age-frequency- and comorbidity-matched mild symptomatic patients. They found
Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase.
In other words, 40% of the asymptomatic patients and 13% of patients with symptoms lost all of the longer lived IgG antibodies (seronegative) by the point of recovery. This may mean they have no immunity against reinfection.
The herd immunity threshold (HIT), is the level of infection of a population by a disease, that is high enough that further spread is reduced to the point that the disease will die out.
Based on experience with other epidemics, the HIT for SARS-CoV-2 was estimated to be as high as 70-80%. A new study out of Oxford suggests that it may be much lower for COVID-19.
that HIT may be greatly reduced if a fraction of the population is unable to transmit the virus due to innate resistance or cross-protection from exposure to seasonal coronaviruses.
Given the mounting evidence that exposure to seasonal coronaviruses offers protection against clinical symptoms ( 9 ) , it would be reasonable to assume that exposure to SARS-CoV-2 itself would confer a significant degree of clinical immunity. Thus, a second peak may result in far fewer deaths, particularly among those with comorbidities in the younger age classes.Lourenço et al. (2020)
Supporting this research is work done by Le Bert, et al (2020) who found that individuals with memory T cells created by other corona virus infections exhibited
the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein.
infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP.Le Bert et al (2020).
This T cell immunity to SARS-CoV was found still robust after 17 years.
The upshot is that a large percentage of the population may have a degree of T cell-based immunity to the family of corona viruses. this presumably allows for healthy individuals to mount a defence against SARS-CoV-2 infection that controls it before a symptomatic stage is reached.
The two papers present a mechanism for achieving her immunity at lower levels than for other diseases, contingent on a population that is commonly subjected to other corona viruses such as the common cold. This might be expected to correlate to regional variations were in northern latitudes, colds are more frequent.
Length of Immunity
A study out of the Imperial College in England has found antibody immunity may last only a few months. A new study pending review by Dan et al. (2020) found that IgG antibody titres were higher after 6 months than 1 month but “CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months“.
A study by Krammer et al (2021) found that persons with antibodies from a past SARS-CoV-2 infection have their antibody level boosted to that or greater than that of persons given the second vaccine dose. The implication is that a single dose is sufficient.
Canada has created a COVID-19 Immunity Task Force and Secretariat. Thr Secretariat has mainly an administrative and governance function. The Task Force itself will fund development of serologic testing a nd testing programs to answer the questions around immunity to the SARS-COV-2 virus such as length of conferred immunity.
The Vaccine Development Process
The CDC in the US breaks down vaccine development into 6 stages. The third stage, ‘Clinical development’, is the one for human trials. It is described as:
a three-phase process. During Phase I, small groups of people receive the trial vaccine. In Phase II, the clinical study is expanded and vaccine is given to people who have characteristics (such as age and physical health) similar to those for whom the new vaccine is intended. In Phase III, the vaccine is given to thousands of people and tested for efficacy and safety.CDC reference 1.
Widespread research and development of a SARS-CoV-2 virus vaccine is being carried o across the globe. Normally the development of a vaccine goes through multiple stages, described above, taking a year to 18 months or more.
This section reviews results of human trials, latest to oldest.
The Callow study of another corona virus is suggestive but not definitive that long-term immunity is not likely. The study by Long, Tang, et al. suggests that it could be relatively short in length, especially for asymptomatic infections.
These are early results but raise the concern that an effective vaccine may not be possible.
- Centers for Disease Control and Prevention (CDC). Vaccine Testing and the Approval Process.
- 2A “Novel” Breakthrough? New Studies Show Memory T-Cells Offer Long Term And Pre-Existing COVID Immunity. unprocessed
- Jose Mateus1, Alba Grifoni1, Alison Tarke, et al. xResearch Article Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans. Science 04 Aug 2020: DOI: 10.1126/science.abd3871 unprocessed
- Good News! Up To 50% Of Us May Be ‘Pre-Immune’ To Covid-19 unprocessed
- Callow, K.A., et al. The time course of the immune response to experimental coronavirus infection of man. PMID: 2170159PMCID: PMC2271881DOI: 10.1017/s0950268800048019.
- Heaton, P.M. The Covid-19 Vaccine-Development Multiverse. NEJM. July 14, 2020; DOI: 10.1056/NEJMe2025111.
- Jackson, L.A., et al. An mRNA Vaccine against SARS-CoV-2 — Preliminary Report. N Engl J Med July 14, 2020; DOI: 10.1056/NEJMoa2022483.
- Le Bert, N., Tan, A.T., Kunasegaran, K. et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature (2020). https://doi.org/10.1038/s41586-020-2550-z.
- Long, Q., Liu, B., Deng, H. et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 26, 845–848 (2020); https://doi.org/10.1038/s41591-020-0897-1.
- Long, Q., Tang, X., Shi, Q. et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med (2020); https://doi.org/10.1038/s41591-020-0965-6.
- Lourenço, J., Pinotti, F., Thompson, C., et al. The impact of host resistance on cumulative mortality and the threshold of herd immunity for SARS-CoV-2. medRxiv preprint doi: https://doi.org/10.1101/2020.07.15.20154294.
- Seow, J., Graham, C., Merrick, B., et al. Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infection. medRxiv. 2020.07.09.20148429; doi: https://doi.org/10.1101/2020.07.09.20148429.
- Alistair Smout. UK study finds evidence of waning antibody immunity to COVID-19 over time. Reuters, October 26, 2020.
- Dan, J.M., Mateus, J., Kato, Y., et al. Immunological memory to SARS-CoV-2 assessed for greater than six months after infection. bioRxiv, November 15, 2020; doi: https://doi.org/10.1101/2020.11.15.383323.
- Crotty S. COVID 19 Vaccine Deep Dive: Safety, Immunity, RNA Production, w Shane Crotty, PhD (Pfizer / Moderna). YouTube. December 17, 2020.
- Krammer F, Srivastava K, et al. Robust spike antibody responses and increased reactogenicity in seropositive individuals after a single dose of SARS-CoV-2 mRNA vaccine. medRxiv. January 29; doi: https://doi.org/10.1101/2021.01.29.21250653.