Longevity of Middle East Respiratory Syndrome Coronavirus Antibody Responses in Humans, Saudi Arabia

Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV–specific neutralizing antibodies were detected for 6 years postinfection.

Understanding the immune response to Middle East respiratory syndrome coronavirus (MERS-CoV) is crucial for disease prevention and vaccine development. We studied the antibody responses in 48 human MERS-CoV infection survivors who had variable disease severity in Saudi Arabia. MERS-CoV-specifi c neutralizing antibodies were detected for 6 years postinfection. diagnosis, MERS-CoV antibody responses were measured 2-6 years postinfection.
Survivors who had mild, moderate, and severe disease had the following median (IQR) titers for neu-  (Figure, panel  B). We found no major decrease in neutralizing antibody titers over 6 years (Figure, panel A). Survivors who had moderate and severe disease had higher titers than survivors who had mild disease over 6 years (Figure, panel B).

Conclusions
At 6 years postinfection, we detected antibody responses in 100% of MERS survivors who had severe Figure. Neutralization antibody titers in Middle East respiratory syndrome (MERS) convalescent-phase serum samples measured 2--6 years postinfection, Saudi Arabia. Three groups (patients who had mild, moderate, or severe MERS) were enrolled in this study, and serum samples were collected for neutralizing antibody detection (median focus reduction neutralization test titer) at the indicated times after recovery. The cutoff value was 1:20. Median titers of neutralizing antibody (red dots) and interquartile range (blue bars) were measured according to years postinfection (panel A) and disease severity (panel B). There was no major decrease in neutralizing antibodies over 6 years postinfection. Survivors who had moderate and severe disease had higher neutralizing antibody titers then survivors who had mild disease. Mod, moderate; Sev, severe.
or moderate disease and in 50% of survivors who had mild disease, demonstrating durability of the MERS-CoV-specific antibody response. Because we did not measure MERS-CoV-specific T lymphocyte responses, the number of MERS survivors who had detectable immune responses was probably underestimated. T-cell responses were detected in several MERS survivors who had negative antibody responses at 6 months postinfection (9). The results are consistent with those of previous studies, which the association between disease severity and decrease of antibody response in MERS survivors over time (10). Similar results were described after the SARS epidemic. SARS survivors had persistent antibody responses for 3 years postinfection, and a decrease by 6 years postinfection (11,12). However, a recent study indicated that low levels of SARS-CoV-specific antibody could be detected in some survivors at 12 years postinfection (X. Guo et al., Sun Yat-sen University, pers. comm., 2020 Jan 1).
In this study, we performed ELISA and neutralizing antibody assays for all cases. Although cases of severe disease showed good concordance between the 2 assays, some cases of mild or moderate disease had a negative ELISA result and a positive neutralizing test result. Similar results were observed in camel workers who had asymptomatic MERS-CoV infections, most of whom who had negative ELISA results but detectable neutralizing antibody titers (13). Negative ELISA results might reflect either insensitivity of the assay or high cutoff values established by the manufacturer to minimize the rate of false-positive results. In either instance, these results suggest that negative ELISA results should be read with caution in some settings.
A limitation of our study was the small number of cases of moderate or severe disease and a lack of serial samples for nearly all patients. It will also be useful to determine whether levels of antibody would be protective if MERS-CoV reinfection occurred. In conclusion, we showed that virus-specific neutralizing antibodies are detectable in most MERS survivors for >6 years, consistent with durable immunity against the virus.