Monday, July 13, 2020

Kings College: Longitudinal Evaluation & Decline of Antibody Responses in SARS-CoV-2 infection


Three months ago, in COVID-19: From Here To Immunity, we looked at the messy, highly inconvenient, and admittedly limited evidence suggesting that lifetime - or even prolonged - immunity following SARS-CoV-2 infection might not be as robust as many people are counting on. 

One of the examples I mentioned was a 2016 study (see EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors) that found limited and short-lived antibody titers among a small cohort of mild MERS-CoV survivors.

Specifically, the study looked at 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.
A year later (May 2017) a report in the EID Journal: MERS-CoV Antibody Response After 1 Year, followed and tested 11 survivors of South Korea's 2015 MERS outbreak at 6 and 12 months, and like earlier studies, found that those with mild illness saw significant reduction in antibody titers over a year's time.

The main thrust of that particular blog, however, was an opinion piece published by the New York Times by Dr. Marc Lipsitch that went over the still slim and sometimes conflicting evidence for acquired immunity from COVID-19 infection, along with some of the challenges of creating a vaccine.

Since then we've revisited the topic of limited acquired (either via natural infection or from a vaccine) immunity to SARS-CoV-2 a number of times (see here, here, and here) - and while far from conclusive - what once was viewed as almost virological heresy is now becoming a mainstream concern. 

To this debate we can add a new (pre-print) study out of King's College London, that finds - as with the above mentioned MERS-CoV studies - that `the magnitude of the nAb response is dependent upon the disease severity'. They also found a significant percentage of mild cases saw their nAb titers drop to near baseline within 60 days post-infection. 

A transient immune response has ramifications both for re-infection risks (lowering the likelihood of achieving `herd' immunity) and vaccine effectiveness and the duration of its protection. 

That said, it should be noted that nAb titers aren't the only measure of potential post-infection immunity, as the role of T-Cells in fighting this virus is poorly understood.  Still, these results give pause, as it suggests many people - particularly those who had a mild first illness - may become susceptible to re-infection within months of recovery. 

Jeffrey Seow, Carl Graham, Blair Merrick, Sam Acors, Kathryn J.A. Steel, Oliver Hemmings, Aoife O'Bryne, Neophytos Kouphou, Suzanne Pickering, Rui Galao, Gilberto Betancor, Harry D Wilson, Adrian W Signell, Helena Winstone, Claire Kerridge, Nigel Temperton, Luke Snell, Karen Bisnauthsing, Amelia Moore, Adrian Green, Lauren Martinez, Brielle Stokes, Johanna Honey, Alba Izquierdo-Barras, Gill Arbane, Amita Patel, Lorcan OConnell, Geraldine O Hara, Eithne MacMahon, Sam Douthwaite, Gaia Nebbia, Rahul Batra, Rocio Martinez-Nunez, Jonathan D. Edgeworth, Stuart J.D. Neil, Michael H. Malim, Katie Doores

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.
Antibody (Ab) responses to SARS-CoV-2 can be detected in most infected individuals 10-15 days following the onset of COVID-19 symptoms. However, due to the recent emergence of this virus in the human population it is not yet known how long these Ab responses will be maintained or whether they will provide protection from re-infection. 
Using sequential serum samples collected up to 94 days post onset of symptoms (POS) from 65 RT-qPCR confirmed SARS-CoV-2-infected individuals, we show seroconversion in >95% of cases and neutralizing antibody (nAb) responses when sampled beyond 8 days POS.
We demonstrate that the magnitude of the nAb response is dependent upon the disease severity, but this does not affect the kinetics of the nAb response.
Declining nAb titres were observed during the follow up period. Whilst some individuals with high peak ID50 (>10,000) maintained titres >1,000 at >60 days POS, some with lower peak ID50 had titres approaching baseline within the follow up period. A similar decline in nAb titres was also observed in a cohort of seropositive healthcare workers from Guy′s and St Thomas′ Hospitals.
We suggest that this transient nAb response is a feature shared by both a SARS-CoV-2 infection that causes low disease severity and the circulating seasonal coronaviruses that are associated with common colds. This study has important implications when considering widespread serological testing, Ab protection against re-infection with SARS-CoV-2 and the durability of vaccine protection. 
          (Continue . . . . )

The standard caveats apply; this study is based on a limited cohort of cases,  it hasn't been peer reviewed, and there is still much we don't understand about the human immune response to SARS-CoV-2 infection. 

That said, assuming these results hold up, it suggests that this novel coronavirus may be far harder to corral (either via herd immunity or a vaccine) than many had initially hoped. 

Stay tuned.