Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1.

Middle East Respiratory Syndrome Coronavirus: A Review

“…MERS-CoV infection is confirmed by Real Time Polymerase Chain Reaction (RT-PCR) targeting two or three available RNA targets or alternatively by sequencing (12)(13)(14)(15). When the molecular methods of diagnosis are negative, serology can be used to detect specific antibodies in patients and contacts in available human and animal samples.…”

“…Although human to human transmission does occur, it seems that the transmission ability of the virus is limited to family contacts and health care settings (9,10). However a large proportion of cases had caught the disease by a "community acquired" form with suspected zoonotic transmission (1,12,13). As of October 2014, globally 855 laboratory-confirmed cases of infection with MERS-CoV, including at least 333 related deaths, have officially been reported to the World Health Organization (WHO) (14).…”

“…The novel virus was named Middle East Respiratory Syndrome Coronavirus (MERS-CoV). Human to human transmission of MERS-CoV has been documented in several clusters of cases, including among family members and in hospital facilities (5)(6)(7)(8)(9)(10)(11)(12)(13). Although human to human transmission does occur, it seems that the transmission ability of the virus is limited to family contacts and health care settings (9,10).…”

“…Most reported cases presented with severe respiratory distress and pneumonia. Animal sources and zoonotic transmission was suggested (11)(12)(13). The novel virus was named Middle East Respiratory Syndrome Coronavirus (MERS-CoV).…”

“…neighbor countries (10)(11)(12)(13). In retrospective reports, similar cases were identified in a hospital outbreak occurred in Jordan in June 2012 (10).…”