Sequential Emergence and Wide Spread of Neutralization Escape Middle East Respiratory Syndrome Coronavirus Mutants, South Korea, 2015

Abstract

The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several “superspreading” events. Previously, we reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak. To assess the potential association of spike mutations with superspreading events, we collected virus genetic information reported during the outbreak and systemically analyzed the relationship of spike sequences and epidemiology. We found sequential emergence of the spike mutations in 2 superspreaders. In vivo virulence of the mutant viruses seems to decline in human patients, as assessed by fever duration in affected persons. In addition, neutralizing activity against these 2 mutant viruses in serum samples from mice immunized with wild-type spike antigen were gradually reduced, suggesting emergence and wide spread of neutralization escapers during the outbreak.

Drug-resistant tuberculosis in eastern Europe and central Asia: a time-series analysis of routine surveillance data

“…By contrast, several studies done after the 2015 MERS outbreak in South Korea yielded important epidemiological, clinical, virological, and management outcome data. 8 MERS-CoV sequence variants were detected during the South Korean outbreak, with some mutations incorporated into the circulating virus. Remarkably, the most extensively studied mutations, which occurred in the surface glycoprotein were not predicted.…”

“…Remarkably, the most extensively studied mutations, which occurred in the surface glycoprotein were not predicted. 8 The surface glycoprotein is crucial for virus entry and during the severe acute respiratory syndrome epidemic it evolved to bind more tightly to its cellular receptor. By contrast, changes detected in MERS-CoV-surface glycoprotein appeared to decrease binding and were expected to decrease virulence and transmissibility; 8 however, these changes could be beneficial to the MERS-CoV by facilitating evasion of the antibody response.…”

“…7 By contrast, drug-resistant tuberculosis as a proportion of tuberculosis increased between two national surveys in 2001 and 2012, primarily driven by an increase in rifampicin mono-resistant tuberculosis. 8 Systematic reviews suggest an association between HIV and drug-resistant tuberculosis, with increased risks of drug-resistant tuberculosis in individuals who are tuberculosis treatment naive, suggesting a stronger association for transmitted resistance than acquired. 9 However, HIV infection has also been associated with increased drug-resistance acquisition during tuberculosis treatment.…”

Confronting the persisting threat of the Middle East respiratory syndrome to global health security

“…4 An upsurge in the number of MERS cases has been seen in Saudi Arabia and Oman, with 189 cases reported between July, 2017, and June, 2018, compared with 126 cases between January and March, 2019. 8 MERS-CoV sequence variants were detected during the South Korean outbreak, with some mutations incorporated into the circulating virus. Importantly, despite many WHO MERS expert group and other stakeholder meetings that have defined priority research needs, major knowledge gaps remain in the epidemiology, transmission, pathogenesis, and phylogenetic evolution of MERS-CoV.…”

“…3 Worryingly, although MERS-CoV continues to circulate in the Middle East, progress in advancing priority research and development on the epidemiology, rapid diagnostics, treatments, and vaccines, including regional One Health activities 5 have been slow. 8 The surface glycoprotein is crucial for virus entry and during the severe acute respiratory syndrome epidemic it evolved to bind more tightly to its cellular receptor. 6,7 Major opportunities for appropriate longitudinal and cross-sectional studies to fill these gaps from the recurrent community and nosocomial outbreaks of MERS in Saudi Arabia are being missed.…”