Association of Higher MERS-CoV Virus Load with Severe Disease and Death, Saudi Arabia, 2014

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a spectrum of illness. We evaluated whether cycle threshold (Ct) values (which are inversely related to virus load) were associated with clinical severity in patients from Saudi Arabia whose nasopharyngeal specimens tested positive for this virus by real-time reverse transcription PCR. Among 102 patients, median Ct of 31.0 for the upstream of the E gene target for 41 (40%) patients who died was significantly lower than the median of 33.0 for 61 survivors (p=0.0087). In multivariable regression analyses, risk factors for death were age>60 years), underlying illness, and decreasing Ct for each 1-point decrease in Ct). Results were similar for a composite severe outcome (death and/or intensive care unit admission). More data are needed to determine whether modulation of virus load by therapeutic agents affects clinical outcomes.

Keywords: MERS-CoV; Middle East respiratory syndrome coronavirus; Saudi Arabia; virus load; viruses; zoonoses.

Figure 1

Box plot of C_t values for MERS-CoV patients by specimen type, Kingdom of Saudi Arabia, 2014. Box and whiskers plot features are as follows: central line in box is median, bottom line of box is first quartile (25%), top line of box is third quartile (75%), diamond is mean, bottom of whiskers is first quarter minus 1.5 × interquartile range, top of whiskers is third quarter plus 1.5 × interquartile range, and dots are outliers. Groups were compared by using the Kruskal-Wallis test, p<0.0001. C_t , cycle threshold; MERS-CoV, Middle East respiratory syndrome coronavirus; upE, upstream of E gene.

Figure 2

Box plot of C_t values for 102 patients infected with MERS-CoV by severity status. Kingdom of Saudi Arabia, 2014. A) Patients who were alive (n = 61) versus dead (n = 41) at the time of follow-up chart review or phone contact. Wilcoxon rank-sum test, p = 0.0087. B) Patients who had a severe outcome (death or ICU admission, n = 48) versus nonsevere outcome (n = 54). Wilcoxon rank-sum test, p = 0.0036. C) Patients who were admitted to the ICU (n = 36) versus the regular ward (n = 31). Wilcoxon rank-sum test, p = 0.014. D) Among patients who survived, symptomatic (n = 30) versus mildly symptomatic/asymptomatic (n = 31). Wilcoxon rank-sum test, p = 0.08. Box and whiskers plot features are as follows: central line in box is median, bottom line of box is first quartile (25%), top line of box is third quartile (75%), diamond is mean, bottom of whiskers is first quarter minus 1.5 × interquartile range, top of whiskers is third quarter plus 1.5 × interquartile range, and dots are outliers. C_t , cycle threshold; ICU, intensive care unit; MERS-CoV, Middle East respiratory syndrome coronavirus.

Figure 3

Relationship between days since illness onset and upE C_t values for MERS-CoV from nasopharyngeal swabs, Kingdom of Saudi Arabia, 2014. C_t, cycle threshold; MERS-CoV, Middle East respiratory syndrome coronavirus; upE, upstream of E gene.