Factors Associated With Viral Load Kinetics of Middle East Respiratory Syndrome Coronavirus During the 2015 Outbreak in South Korea

Abstract

We conducted a retrospective study of Middle East respiratory syndrome coronavirus (MERS-CoV) viral load kinetics using data from patients hospitalized with MERS-CoV infection between 19 May and 20 August 2015. Viral load trajectories were considered over the hospitalization period using 1714 viral load results measured in serial respiratory specimens of 185 patients. The viral load levels were significantly higher among nonsurvivors than among survivors (P = .003). Healthcare workers (P = .001) and nonspreaders (P < .001) had significantly lower viral loads. Viral RNA was present on the day of symptom onset and peaked 4-10 days after symptom onset.

Keywords: Middle East respiratory syndrome coronavirus; healthcare-associated infections; infectious disease transmission; viral load; virus shedding.

Figure 1.

Time to confirmation of Middle East respiratory syndrome coronavirus (MERS-CoV) infection according to the time since symptom onset; incubation period according to the time since exposure; and viral load levels according to the time since symptom onset in 185 patients with laboratory-confirmed MERS-CoV infection. A, Kaplan–Meier plot of the time from symptom onset until confirmation of diagnosis of MERS-CoV infection on real-time reverse-transcription polymerase chain reaction (rRT-PCR). B, Reverse Kaplan–Meier plot of the incubation period according to survivor status. The x-axis shows the time since exposure to infection, and the y-axis shows the proportion of patients with MERS-CoV detectable on rRT-PCR, stratified by survivor status. The nonsurvivors (fatal cases) had a significantly shorter incubation period than the survivors (P = .0491, log-rank test). By day 5 after exposure to infection, 45% of the nonsurvivors and 30% of the survivors had MERS-CoV detectable on rRT-PCR. The median incubation period was 4.3 days in the nonsurvivors and 6.0 days in the survivors. C, Mean viral load at 1-day intervals. The error bars show the standard deviation. Viral load levels peaked 2–4 days after symptom onset, after which they gradually declined.

Figure 2.

Comparison of viral load levels in 185 patients with laboratory-confirmed Middle East respiratory syndrome coronavirus infection according to the time since symptom onset by vital status (survivors and nonsurvivors) (A), emergency room (ER) admission (B), age (C), and comparison of viral load levels by spreader status (D). In A–C, the points indicate the mean viral load level and the error bars indicate the standard deviation. In D, patients were classified according to the number of contacts who became infected during the 11 days after symptom as super-spreaders (≥5 contacts infected, n = 5), usual spreaders (<5 contacts infected, n = 17), and nonspreaders (0 contacts infected, n = 163). The box-and-whisker plots show the mean (diamond), median (bar) quartiles (top and bottom of the boxes), and range of the viral loads. P values were determined using a post hoc (Tukey) test for viral load according to spreader grade, and adjusted by age. *P<.05; **P<.001; ***P<.001.