Epidemiology of a Novel Recombinant Middle East Respiratory Syndrome Coronavirus in Humans in Saudi Arabia

Abstract

Background: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory illness in humans. Fundamental questions about circulating viruses and transmission routes remain.

Methods: We assessed routinely collected epidemiologic data for MERS-CoV cases reported in Saudi Arabia during 1 January-30 June 2015 and conducted a more detailed investigation of cases reported during February 2015. Available respiratory specimens were obtained for sequencing.

Results: During the study period, 216 MERS-CoV cases were reported. Full genome (n = 17) or spike gene sequences (n = 82) were obtained from 99 individuals. Most sequences (72 of 99 [73%]) formed a discrete, novel recombinant subclade (NRC-2015), which was detected in 6 regions and became predominant by June 2015. No clinical differences were noted between clades. Among 87 cases reported during February 2015, 13 had no recognized risks for secondary acquisition; 12 of these 13 also denied camel contact. Most viruses (8 of 9) from these 13 individuals belonged to NRC-2015.

Discussions: Our findings document the spread and eventual predominance of NRC-2015 in humans in Saudi Arabia during the first half of 2015. Our identification of cases without recognized risk factors but with similar virus sequences indicates the need for better understanding of risk factors for MERS-CoV transmission.

Keywords: MERS; MERS epidemiology; MERS phylogeny; MERS transmission; Middle East respiratory syndrome; Saudi Arabia; coronavirus; recombinant.

Figure 1.

Phylogeny of Middle East respiratory syndrome coronavirus (MERS-CoV) spike sequences. Phylogenetic analysis of the MERS-CoV spike gene coding region (4062 nucleotides) obtained from 99 cases in this study and 251 previously published sequences available in GenBank. Major clades A and B are indicated by vertical bars. Figure 1 continued. The novel subclade (NRC-2015) is repositioned for clarity. Spike gene sequences obtained in this study are marked with solid circles; red circles indicate samples with available genome sequences (Supplementary Figure 1). The tree was constructed by the neighbor-joining method, and bootstrap resampling values (1000 replicates) ≥70% are indicated above the respective nodes. Numbers in brackets following some strain identifiers are the number of identical sequences with the same location and sample collection time. The scale bar shows the genetic distance as nucleotide substitutions per site. To compare persistence and geographic distribution of NRC-2015 with other viruses identified during 2012–2015, we assigned virus sequences to different subclades (depicted in color), based on previously described clades [19, 28–30].

Figure 2.

Middle East respiratory syndrome coronavirus (MERS-CoV) cases reported by the Saudi Arabia Ministry of Health (MoH) during 1 January–30 June 2015. A, MERS-CoV cases, by clade and week of illness onset. B, Sequenced viruses, by clade and month of illness onset. The 216 cases reported by the MoH during 1 January–30 June 2015 are included. These graphs do not include the single sequence from the individual with no recognized symptoms who did not meet the case definition. NRC-2015 was defined using the spike gene phylogenies (Figure 1).

Figure 3.

Map of Middle East respiratory syndrome coronavirus (MERS-CoV) cases, by subclade and region of Saudi Arabia. The 216 cases reported by the Saudi Arabia Ministry of Health during 1 January–30 June 2015, are included. This map does not include the single sequence from the individual with no recognized symptoms who did not meet the case definition. NRC-2015 was defined using the spike gene phylogenies (Figure 1).

Figure 4.

Geotemporal distribution of Middle East respiratory syndrome coronavirus (MERS-CoV) clades in Saudi Arabia during 1 January 2013–30 June 2015. For human-derived sequences in each subclade within the broader clade B (as defined using the spike gene phylogenetic analysis in Figure 1), we used GenBank to determine length of persistence, using the earliest and most recent date of detection (A), and we determined geographic distribution, based on city of detection within Saudi Arabia (B). ^a2015 depicts clades detected through 30 June 2015.