Since the earliest days of the COVID pandemic, the question over the durability of acquired immunity following SARS-CoV-2 infection and recovery has been a matter of considerable debate (see April 2020's COVID-19: From Here To Immunity).
While lasting immunity is often a product of some viral infections - like measles and mumps - in other cases, immunity can wane over time.
And over the past few years we'd seen warning signs regarding lasting immunity from human coronavirus infections.
- In April of 2016, in EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors, we looked at a study that tested 9 Health care workers who were infected during the 2014 Jeddah outbreak (2 severe pneumonia, 3 milder pneumonia, 1 URTI, and 3 asymptomatic), that found only those with severe pneumonia still carried detectable levels of antibodies 18 months later.
- In Fenner and White's Medical Virology (Fifth Edition - 2017),, the authors describe the clinical features of seasonal human coronaviruses (hCoVs) in Chapter 31:
The typical coronavirus “common cold” is mild and the virus remains localized to the epithelium of the upper respiratory tract and elicits a poor immune response, hence the high rate of reinfection. There is no cross-immunity between human coronavirus-229E and human coronavirus-OC43, and it is likely that new strains are continually arising by mutation selection.
While confirmed COVID reinfections remained elusive over the summer of 2020, we saw a number of studies emerge warning of a limited antibody response in some recovered patients.
By fall, lab confirmed COVID reinfections were beginning to emerge (see HKU Med Announces 1st Documented Reinfection With SARS-CoV-2), and by the end of the year we began to see secondary waves of infection in regions previously battered by COVID, suggesting a high rate of reinfection (see The Lancet: Resurgence of COVID-19 in Manaus, Brazil, Despite High Seroprevalence).EID Journal: Antibody Profiles According to Mild or Severe SARS-CoV-2 Infection
CDC Clarifies: Recovered COVID-19 Cases Are Not Necessarily Immune To Reinfection
Imperial College London: (REACT) SARS-CoV-2 Antibody Prevalence Study - England
Kings College: Longitudinal Evaluation & Decline of Antibody Responses in SARS-CoV-2 infection
In recent months we've seen a population based study out of Denmark (see Denmark SSI: Assessment of Protection Against Reinfection with SARS-CoV-2) that calculated the average person is about 80% protected - at in the short term - against reinfection with COVID-19.
But, among those aged 65 and over, that protection was estimated to be only 47%.
Nine days ago, in UK NERVTAG Report On Immunity After Natural COVID Infection, we saw a similar assessment, where they suggested that close to 20% of those under the age of 65 may be susceptible to symptomatic reinfection within the first 7 months.
They also warn that: Protection against SARS-CoV-2 infection, disease, and transmission may be diminished by antigenic changes in variant viruses (high confidence).
To this growing body of evidence we can add another (pre-print) study, from the University of Oxford, that find a wide variance in post-infection immunity based on both the severity of the original infection, and individual host factors.
The bottom line: Anyone banking on long-term protection from a previous bout of COVID - particularly in the face of emerging COVID variants - may be severely disappointed.
First some excerpts from a press release from Oxford University, followed by a link and the abstract to the paper.
Latest data on immune response to COVID-19 reinforces need for vaccination, says Oxford-led study
A new study led by the University of Oxford has found that previous infection, whether symptomatic or asymptomatic, does not necessarily protect you long-term from COVID-19, particularly against new Variants of Concern.
The Protective Immunity from T cells to COVID-19 in Health workers study (PITCH) – conducted in collaboration with the universities of Liverpool, Sheffield, Newcastle and Birmingham with support from the UK Coronavirus Immunology Consortium – examined how the immune system responds to COVID-19 in 78 healthcare workers who had experienced either symptomatic or asymptomatic disease (66 vs 12). An additional eight patients who experienced severe disease were included for comparison.
Blood samples were taken monthly from one to six months post infection to examine different elements of the immune response. This included different types of antibodies – such as Spike-specific and Nucleocapsid-specific antibodies produced to target different parts of the virus, alongside B cells that manufacture antibodies and keep the body’s memory of the disease, and several types of T cell.
The preprint report posted on Research Square details a highly complex and variable immune response following COVID-19 infection.
Dr Christina Dold of the Oxford Vaccine Group and study author said: ‘Our study is one of the most comprehensive accounts of the immune response following COVID-19 in both symptomatic and asymptomatic individuals. We found that individuals showed very different immune responses from each other following COVID-19, with some people from both the symptomatic and asymptomatic groups showing no evidence of immune memory six months after infection or even sooner. Our concern is that these people may be at risk of contracting COVID-19 for a second time, especially with new variants circulating. This means that it is very important that we all get the COVID vaccine when offered even if you think you may have previously had COVID-19.’
(SNIP)
While the majority of people who had symptomatic disease did have measurable immune responses at six months post infection, a significant minority (17/66; 26%) did not.
The vast majority of people who experienced asymptomatic disease (11/12; 92%) did not exhibit a measurable immune response at six months post infection.
This implies that people who have previously been infected with COVID-19 should not assume they are automatically protected against reinfection and highlights the importance of everyone getting their COVID vaccination when they are offered it.
(Continue . . . )
RESEARCH ARTICLE
Divergent trajectories of antiviral memory after SARS-Cov-2 infection
Adriana Tomic*, Donal T. Skelly*, Ane Ogbe*, Daniel O'Connor*, Matthew Pace, Emily Adland, Frances Alexander, Mohammad Ali, Kirk Allott, M. Azim Ansari, Sandra Belij-Rammerstorfer , Sagida Bibi, Luke Blackwell, Anthony Brown, Helen Brown, Breeze Cavell, Elizabeth A. Clutterbuck, Thushan I de Silva, David Eyre, Amy Flaxman, James Grist, Carl-Philipp Hackstein, Rachel Halkerston, Adam C. Harding, Jennifer Hill, Tim James, Cecilia Jay, Síle A. Johnson, Barbara Kronsteiner, Yolanda Lie, Aline Linder, Stephanie Longet, Spyridoula Marinou, Philippa C. Matthews, Jack Mellors, Christos Petropoulos, Patpong Rongkard, Cynthia Sedik, Laura Silva-Reyes, Holly Smith, Lisa Stockdale, Stephen Taylor, Stephen Thomas, Timothy Tipoe, Lance Turtle, Vinicius Adriano Vieira, Terri Wrin, OPTIC Clinical Group, PITCH Study Group, C-MORE Group, Andrew J. Pollard, Teresa Lambe, Christopher P. Conlon, Katie Jeffery, Simon Travis, Philip J. Goulder, John Frater, Alexander J. Mentzer, Lizzie Stafford, Miles W. Carroll, William S. James, Paul Klenerman#, Eleanor Barnes#, Christina Dold#, Susanna J. Dunachie#
DOI:
10.21203/rs.3.rs-612205/v1
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Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is normally controlled by effective host immunity including innate, humoral and cellular responses. However, the trajectories and correlates of acquired immunity, and the capacity of memory responses months after infection to neutralise variants of concern - which has important public health implications - is not fully understood.To address this, we studied a cohort of 78 UK healthcare workers who presented in April to June 2020 with symptomatic PCR-confirmed infection or who tested positive during an asymptomatic screening programme and tracked virus-specific B and T cell responses longitudinally at 5-6 time points each over 6 months, prior to vaccination. We observed a highly variable range of responses, some of which - T cell interferon-gamma (IFN-γ) ELISpot, N-specific antibody waned over time across the cohort, while others (spike-specific antibody, B cell memory ELISpot) were stable.In such cohorts, antiviral antibody has been linked to protection against re-infection. We used integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling Over Night) to explore this heterogeneity and to identify predictors of sustained immune responses. Hierarchical clustering defined a group of high and low antibody responders, which showed stability over time regardless of clinical presentation. These antibody responses correlated with IFN-γ ELISpot measures of T cell immunity and represent a subgroup of patients with a robust trajectory for longer term immunity.Importantly, this immune-phenotype associates with higher levels of neutralising antibodies not only against the infecting (Victoria) strain but also against variants B.1.1.7 (alpha) and B.1.351 (beta). Overall memory responses to SARS-CoV-2 show distinct trajectories following early priming, that may define subsequent protection against infection and severe disease from novel variants.
The durability of protection offered by vaccines - particularly against newer variants - is another issue, and one that has yet to be fully explored.
Vaccines are believed, however, to illicit a broader immune response than natural infection, and boosters can be used to extend and improve their protection.
While there may be no perfect protection against reinfection, having had both COVID and the vaccine, I'll take the vaccine over the infection any day.
