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.
This waning antibody response in all but the most severely affected patients raised a number of interesting, and potentially serious, questions.
- Are those who only experienced mild or moderate illness at risk of re-infection?
- Would convalescent plasma donated by those without severe illness be less or ineffective?
- Does this skew (under count) the community seroprevalence studies we've seen coming out of Saudi Arabia and Kenya?
- How will all of this play into the development of a MERS-CoV vaccine (for camels or humans)?
Today we've a new study that builds on, and reinforces, some of what has been reported previously Researchers 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.
Volume 23, Number 7—July 2017
MERS-CoV Antibody Responses 1 Year after Symptom Onset, South Korea, 2015
Pyoeng Gyun Choe1, R.A.P.M. Perera1, Wan Beom Park, Kyoung-Ho Song, Ji Hwan Bang, Eu Suk Kim, Hong Bin Kim, Long Wei Ronald Ko, Sang Won Park, Nam-Joong Kim, Eric H.Y. Lau, Leo L.M. Poon, Malik Peiris Comments to Author , and Myoung-don Oh
We investigated the kinetics of the Middle East respiratory syndrome coronavirus (MERS-CoV) neutralizing and spike protein antibody titers over the course of 1 year in 11 patients who were confirmed by reverse transcription PCR to have been infected during the outbreak in South Korea in 2015. Robust antibody responses were detected in all survivors who had severe disease; responses remained detectable, albeit with some waning, for < 1 year.
The duration of viral RNA detection (but not viral load) in sputum significantly correlated with the antibody response magnitude. The MERS S1 ELISA antibody titers correlated well with the neutralizing antibody response. Antibody titers in 4 of 6 patients who had mild illness were undetectable even though most had evidence of pneumonia. This finding implies that MERS-CoV seroepidemiologic studies markedly underestimate the extent of mild and asymptomatic infection. Obtaining convalescent-phase plasma with high antibody titers to treat MERS will be challenging.
Middle East respiratory syndrome (MERS) remains a disease of global public health concern for which no proven specific countermeasures are available. As of December 5, 2016, ≈1,800 laboratory-confirmed cases have been reported (1). MERS coronavirus (MERS-CoV) is an enzootic pathogen present in dromedary camels in many parts of the world, including the Middle East, Iran, Pakistan, and Africa (2,3).
Zoonotic infections have been repeatedly reported on the Arabian Peninsula and have led to large nosocomial outbreaks. One notable example occurred in South Korea in 2015, initiated by a traveler returning home from the Arabian Peninsula (4). The infection in this traveler led to an outbreak of 186 cases and 36 deaths that had a substantial impact on the local economy. A cohort of 17 patients from this outbreak was intensively followed up to obtain detailed clinical, immunologic, and virologic characterization of their disease course (5,6).
The kinetics of the serologic responses during the acute phase have already been reported, and they showed that robust but delayed antibody responses could be detected in patients who were more severely ill (7). Another study reported a significant linear correlation between the log10 viral loads and the serologic response in the acute phase of illness (8). The kinetics of the long-term serologic responses to MERS-CoV infections is poorly understood and remains of clinical interest. We report the results of a 1-year follow-up on the antibody responses in 11 of these patients.
In conclusion, our findings support and extend the research of others. We suggest that serologic tests for MERS-CoV antibodies can only identify some of the patients who have had MERS-CoV infections. Serologic responses to this virus are variable, not robust, and often undetectable when disease is mild. Thus, MERS-CoV seroepidemiologic studies will only detect a fraction of infections that are occurring in a population and will probably markedly underestimate the extent of mild infection that is taking place.
Our findings also show that the MERS S1 ELISA is as good as neutralization tests at detecting antibodies a year after infection, but positive ELISA results do require confirmation with neutralization tests if false positives are to be avoided in seroepidemiologic assays (M. Peiris, unpub. data).
Convalescent-phase plasma can be harvested for many months to a year after disease from patients surviving MERS-CoV infection, but plasma with a high antibody titer is only likely to be obtained during the first few months of convalescence from persons who had severe disease. Because patients during this time frame are likely to be frail, this approach will be challenging.
Dr. Choe is a clinical scientist at Seoul National University Hospital. His research interests focus on preventing healthcare-associated infection and responding to emerging infectious diseases.
Aside from the practical matter of harvesting convalescent plasma from MERS survivors, and the development of long-lasting vaccines (for camels or humans), the potential skewing of seroprevalence studies (see EID Journal: MERS-CoV Antibodies in Humans, Africa, 2013–2014) due to waning antibodies raises new questions over just how common mild, unidentified MERS infections might be in the community.