Monday, September 14, 2020

Nature Medicine: Seasonal Coronavirus Protective Immunity Is Short-Lasting


While there are a great many unknowns surrounding our COVID-19 pandemic - and what will happen this fall and winter - arguably the biggest centers on the duration of post-infection (or post-vaccination) immunity to SARS-CoV-2 infection. 

The initial assumption - at least promulgated publicly - was once you've recovered from COVID-19, you'd carry long-term, and hopefully, life-time immunity.  

This reassurance made `herd immunity' - either via natural infection or the deployment of a vaccine - an achievable goal.  Once we'd reached some (undetermined) percentage of community immunity, the pandemic would end and life would return to normal. 

The `fly in this ointment' was - while there are indeed many viral infections which leave behind long-lasting immunity - it is far from being universally true.  And we'd seen some limited evidence in the past suggesting that coronaviruses might be exceptions to the rule. 

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.
Perhaps more on point, in 2016's 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.
Those who experienced a milder pneumonia had shorter lived antibody responses (1 out to 10 months, 2 out to 3 months), while the URTI and asymptomatic cases tested negative at 3 months post infection.
All of which made the revelation in late February of a suspected - but far from proven - reinfection of a COVID-19 case in Japan at least plausible (see Osaka Japan: `Recovered' Patient Tests Positive For COVID-19).   At the time, I wrote:
It isn't entirely clear whether this is a relapse, or if the patient may have been re-exposed to and reinfected by the virus, or if the tests used to clear her for discharge simply weren't sensitive enough to pick up a lingering, low grade, infection.

We would see a number of additional potential reinfections over the spring and summer, but it wouldn't be until mid-August that we saw a laboratory confirmed reinfection (see HKU Med Announces 1st Documented Reinfection With SARS-CoV-2) with the novel coronavirus. 

Within days, several more reinfections were confirmed around the globe (see Another SARS-COV-2 Reinfection Report To Ponder (Nevada, United States)). While a proof of concept, we still don't know how common reinfection with SARS-CoV-2 is, or - on average - long long immunity persists post-infection.  

Meanwhile, over the summer we saw a number of additional studies, and cautionary statements from public health agencies, on prolonged post-infection SARS-CoV-2 immunity. 

NEJM: Humoral Immune Response to SARS-CoV-2 in Iceland

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

GAO: A Herd Immunity For COVID-19 Primer

While the jury is still out, the evidence supporting robust and long-lasting protection against SARS-CoV-2 either post-infection or from receipt of a vaccine is less reassuring than it once was.  If people become susceptible to reinfection in a matter of months, then `herd immunity' become far less achievable. 

While it may not end up being directly applicable to SARS-CoV-2, we've a new dispatch, published in Nature Medicine, which attempts to quantify the duration of immunity following infection with seasonal human coronaviruses (hCoVs).  

The authors report that reinfection with hCoVs can occur in as little as 6 months, but becomes common at 12 months.  I've only included the link, and a couple of brief excerpts from a much longer report.  Follow the link to read it in its entirety. 

Brief Communication
Published: 14 September 2020
Seasonal coronavirus protective immunity is short-lasting

Arthur W. D. Edridge, Joanna Kaczorowska, Alexis C. R. Hoste, Margreet Bakker, Michelle Klein, Katherine Loens, Maarten F. Jebbink, Amy Matser, Cormac M. Kinsella, Paloma Rueda, Margareta Ieven, Herman Goossens, Maria Prins, Patricia Sastre, Martin Deijs & Lia van der Hoek 


A key unsolved question in the current coronavirus disease 2019 (COVID-19) pandemic is the duration of acquired immunity. Insights from infections with the four seasonal human coronaviruses might reveal common characteristics applicable to all human coronaviruses. We monitored healthy individuals for more than 35 years and determined that reinfection with the same seasonal coronavirus occurred frequently at 12 months after infection.


Caution should be taken when relying on policies that require long-term immunity, such as vaccination or natural infection to reach herd immunity. Other studies have shown that neutralizing SARS-CoV-2 antibody levels decrease within the first 2 months after infection, especially after mild COVID-19 7,8, and we observed a similar decrease in anti-nucleocapsid antibodies of seasonal coronaviruses (Extended Data Fig. 6).
However, antibodies are only one marker for immunity, which is probably also influenced by B cell- and T cell-mediated immunity. In our study, we monitored reinfections, which can occur only when protective immunity (cellular and/or humoral) is insufficient.
We show that reinfections by natural infection occur for all four seasonal coronaviruses, suggesting that it is a common feature for all human coronaviruses, including SARS-CoV-2. Reinfections occurred most frequently at 12 months after infection, indicating that protective immunity is only short-lived.

          (Continue . . . )


While less-than-permanent immunity doesn't negate the value of a SARS-CoV-2 vaccine, it does mean that even if an effective vaccine can be developed, it may not be the panacea for this pandemic that many have hoped.

As we've discussed previously (see `Forward Looking' & `Aspirational' Vaccine Press Releases) deploying billions of doses of vaccine in the midst of a pandemic is far easier said than done, and won't happen overnight. As with influenza vaccines, it may require regular boosters and reformulations over time, and its effectiveness may vary widely between individuals. 

But even if vaccines aren't fully protective, they may - as with influenza vaccines - reduce the severity of illness.   

While I have reservations over a rushed, 1st-generation vaccine (see Remembering An Emergency Pandemic Vaccine Program That Went Awry), I am hopeful that over time, a safe and effective vaccine can be developed and deployed.  

But vaccine or not, COVID-19 - in one form or another - is likely to become endemic, and a seasonal threat, for years to come.