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Middle East respiratory syndrome coronavirus on inanimate surfaces: A risk for health care transmission

  • Raymond M. Khan
    Correspondence
    Address correspondence to Raymond M. Khan, MD, Intensive Care Department, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, PO Box 22490, Mail code 1425, Riyadh, Saudi Arabia. (R.M. Khan).
    Affiliations
    Intensive Care Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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  • Hasan M. Al-Dorzi
    Affiliations
    Intensive Care Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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  • Sameera Al Johani
    Affiliations
    Pathology and Laboratory Medicine Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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  • Hanan H. Balkhy
    Affiliations
    Infection Control Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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  • Thamer H. Alenazi
    Affiliations
    Infectious Diseases, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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  • Salim Baharoon
    Affiliations
    Intensive Care Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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  • Yaseen M. Arabi
    Affiliations
    Intensive Care Department, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
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      The Middle East Respiratory syndrome coronavirus (MERS-CoV) has been responsible for multiple health care–associated outbreaks. We investigated whether high-touch surfaces in 3 rooms of laboratory-confirmed MERS-CoV patients were contaminated with MERS-CoV RNA. We found 2 out of 51 surfaces were contaminated with MERS-CoV viral genetic material. Hence, environmental contamination may be a potential source of health care transmission and outbreaks. Meticulous environmental cleaning may be important in preventing transmission within the health care setting.

      Key Words

      In September 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) was identified from a patient in Saudi Arabia. As of March 29, 2016, the World Health Organization reported 1,698 laboratory-confirmed MERS cases in 26 countries, with 609 deaths (36%).
      • World Health Organization
      Middle East respiratory syndrome coronavirus (MERS-CoV).
      In its most recent report, the Centers for Disease Control and Prevention has stressed the great importance of personal protective equipment (PPE), source control, and environmental infection control measures to help eliminate the threat of health care–associated outbreaks.
      • Williams H.A.
      • Dunville R.L.
      • Gerber S.I.
      • Erdman D.D.
      • Pesik N.
      • Kuhar D.
      • et al.
      CDC's early response to a novel viral disease, middle east respiratory syndrome coronavirus (MERS-CoV), September 2012–May 2014.
      Most health care–associated MERS-CoV outbreaks has occurred in Saudi Arabia. Although the precise mechanism of human-to-human transmission has not been elucidated, MERS-CoV can be recovered from plastic surfaces after 48 hours at 20°C and 40% relative humidity (RH), and the virus is viable for 8 hours at 30°C and 80% RH and for 24 hours at 30°C and 30% RH.
      • van Doremalen N.
      • Bushmaker T.
      • Munster V.J.
      Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions.
      Further, data from the South Korean outbreak (May 2015) demonstrated that several environmental surfaces frequently touched by laboratory-confirmed MERS patients and health care workers were contaminated by MERS-CoV.
      • Bin S.Y.
      • Heo J.Y.
      • Song M.S.
      • Lee J.
      • Kim E.H.
      • Park S.J.
      • et al.
      Environmental contamination and viral shedding in MERS patients during MERS-CoV outbreak in South Korea.
      Additionally, viral sheading was detected by viral cultures from respiratory secretions up to 25 days postdisease onset.
      • Bin S.Y.
      • Heo J.Y.
      • Song M.S.
      • Lee J.
      • Kim E.H.
      • Park S.J.
      • et al.
      Environmental contamination and viral shedding in MERS patients during MERS-CoV outbreak in South Korea.
      Although MERS-CoV was isolated from numerous high-touch surfaces in 2 Korean hospitals affected by MERS outbreak,
      • Bin S.Y.
      • Heo J.Y.
      • Song M.S.
      • Lee J.
      • Kim E.H.
      • Park S.J.
      • et al.
      Environmental contamination and viral shedding in MERS patients during MERS-CoV outbreak in South Korea.
      such data are lacking in the Middle East. Therefore, the objective of this study was to examine the extent of environmental contamination with MERS-CoV during an outbreak in a Saudi hospital.

      Materials and methods

      The study was performed in the intensive care unit (ICU) at King Abdul-Aziz Medical City, Riyadh, during a MERS-CoV outbreak from September 1-October 5, 2015. The ICU had strict environmental cleaning policies, which included cleaning the rooms at least twice daily using ammonium-based disinfectant and chlorine solution 1:10 or 5,000 ppm, having a checklist, and frequent inspection using fluorescent light or culturing of high-touch areas.
      Three negative-pressure rooms of laboratory-confirmed MERS patients (A, B, and C) were selected for this study (Table 1). The room temperature was 20.0°C-25.0°C, and RH was 30%-40%. The air exchange rate was 12 per hour, and the pressure gradient between the room and its anteroom ranged from 2.5-12.5 Pa. Sixteen high-touch surfaces were evaluated (Table 2): 14 in the patients' room (bedrails, mechanical ventilator, ventilator tubing, sink, garbage bin, monitor, intravenous poles, intravenous pumps, telephone, door knobs, floor, drapes-blinds, air conditioning vent, and shelf of the surgical boom) and 2 outside (computer and medical chart). Environmental samples were collected as described by Julian et al.
      • Julian T.R.
      • Tamayo F.J.
      • Leckie J.O.
      • Boehm A.B.
      Comparison of surface sampling methods for virus recovery from fomites.
      Briefly, a sterile swab premoistened with viral transport media was used to swab each surface (at least 10 cm2) horizontally, vertically, and diagonally for 30 seconds. This procedure was repeated using eluents: 1/4 lactated ringer solution and phosphate buffer solution (PBS). Virus detection was performed using specific real-time reverse-transcription polymerase chain reaction (PCR) assays for the upstream of the envelope gene and the open reading frame 1A. Positive tests were reported as the cycle threshold value for both upstream of the envelope gene (E) and open reading (O) frame 1A.

      Results

      The demographic for the patients are summarized in Table 1. All 3 laboratory-confirmed MERS patients were on mechanical ventilators, with an average PaO2/FiO2 ratio of 196. The mean ICU length of stay and time from last positive tracheal aspirate for MERS-CoV RNA to environmental sampling were 9.3 days and 40 hours, respectively.
      Table 1Characteristic, physiologic, and laboratory variables for the patients in the rooms during environmental sampling
      VariablesPatients
      ABC
      Age, y358530
      SexFemaleMaleMale
      Body mass index, kg/m228.724.937.3
      APACHE II score183115
      Time in room before environmental sampling, d8164
      Time from last positive MERS-CoV to environmental sampling, h242472
      MERS-CoV, Cp/CTE = 17

      O = 18
      E = 20

      O = 20
      E = 34

      O = 35
      FiO2, %553040
      Tidal volume, mL250380450
      PEEP, cm H2O1658
      PaO2/FiO2 ratio152.6269.3166.8
      Leukocyte count, ×109 cells/L14.616.711.6
      Platelet count, ×109 cells/L34589286
      Lactate level, mmol/L1.032.420.58
      Creatinine concentration, µmol/L65117399
      Bilirubin level, µmol/L13.331.912.7
      AST level, U/L4187939
      ALT level, U/L3680820
      NOTE. Cp or CT value is the cycle at which fluorescence achieves a defined threshold. The number of cycles needed for the amplification-associated fluorescence to reach a specific threshold level of detection (CT or Cp value) is inversely correlated to the amount of nucleic acid that was in the original sample. CT  <29 is a strong positive reaction indicative of abundant target nucleic acid in the sample; CT of 30-37 is a positive reaction indicative of moderate amounts of target nucleic acid, and CT of 38-40 is a weak reaction indicative of minimal amounts of target nucleic acid.
      ALT, alanine aminotransferase; APACHE II, Acute Physiology and Chronic Health Evaluation II; AST, aspartate aminotransferase; Cp, crossing point; CT, threshold cycle; E, E-protein gene (upstream of the envelope gene); FiO2, fraction of inspired oxygen; MERS-CoV, Middle East respiratory syndrome coronavirus; O, open reading frame 1b (ORF 1b); PaO2/FiO2, arterial oxygen partial pressure to fractional inspired oxygen; PEEP, positive end expiratory pressure.
      Sixteen surfaces were evaluated in each of the 3 ICU rooms, with 153 environmental samples processed (Table 2). MERS-CoV viral nucleic acid was detected in 2 specimens (PBS as eluent) taken from room C. The positive surfaces were the shelf of the surgical boom and the inside door knob, with cycle threshold values E = 33/O = 31 (positive) and E = 36/O = 0 (intermediate), respectively.
      Table 2Fomites and different isolation reagents
      FomitesRoom A

      (n = 51)
      Room B

      (n = 51)
      Room C

      (n = 51)
      UTM

      Swab
      1/4LRPBSUTM Swab1/4LRPBSUTM

      Swab
      1/4LRPBS
      Inside ICU room
       1Bedrails 1 (head)
       2Bedrails 2 (side)
       3Vent
       4Vent tubing
       5Sink
       6Garbage bins
       7Monitors
       8Intravenous poles
       9Intravenous pumps
       10Telephone
       11Door knob+
       12Floor
       13Drapes-blinds
       14Air vent
       15Surgical boom shelf+
      Outside ICU room
       16Keyboards (computer)
       17Chart
      NOTE. The results of real-time polymerase chain reaction for Middle East respiratory syndrome coronavirus viral RNA from various ICU environmental surfaces and eluents (solvents) used.
      ICU, intensive care unit; PBS, phosphate buffer solution; UTM, universal transport medium; 1/4LR, one-quarter lactate ringers; , negative test result in the room; +, positive test result in the room.

      Discussion

      Our study revealed that MERS-CoV viral RNA was isolated from the environmental surfaces of MERS patients.
      Currently, much remains uncertain about the transmission mechanism responsible for MERS nosocomial outbreaks. It was postulated from the outbreak in Al-Hasa, Saudi Arabia, in May-June 2012 that respiratory droplet and airborne transmission during aerosol-generating procedures were the most likely transmission modes.
      • Assiri A.
      • McGeer A.
      • Perl T.M.
      • Price C.S.
      • Al Rabeeah A.A.
      • Cummings D.A.
      • et al.
      Hospital outbreak of Middle East respiratory syndrome coronavirus.
      However, genetic data from a cluster in Hafr Al-Batin, Saudi Arabia, showed that direct person-to-person contact could not account for all of their cases,
      • Memish Z.A.
      • Cotten M.
      • Watson S.J.
      • Kellam P.
      • Zumla A.
      • Alhakeem R.F.
      • et al.
      Community case clusters of Middle East respiratory syndrome coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: a descriptive genomic study.
      therefore raising the likelihood of an alternate transmission mechanism. Studies on kinetics and patterns of viral excretion indicate that MERS-CoV RNA was isolated from urine and feces 13 and 16 days, respectively, after initial symptoms.
      • Drosten C.
      • Seilmaier M.
      • Corman V.M.
      • Hartmann W.
      • Scheible G.
      • Sack S.
      • et al.
      Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection.
      Viral shedding from respiratory aspirates may persist up to 33 days after illness onset.
      • Poissy J.
      • Goffard A.
      • Parmentier-Decrucq E.
      • Favory R.
      • Kauv M.
      • Kipnis E.
      • et al.
      Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases.
      Prolonged viral shedding
      • Drosten C.
      • Seilmaier M.
      • Corman V.M.
      • Hartmann W.
      • Scheible G.
      • Sack S.
      • et al.
      Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection.
      • Poissy J.
      • Goffard A.
      • Parmentier-Decrucq E.
      • Favory R.
      • Kauv M.
      • Kipnis E.
      • et al.
      Kinetics and pattern of viral excretion in biological specimens of two MERS-CoV cases.
      and survival on surfaces for 48 hours
      • van Doremalen N.
      • Bushmaker T.
      • Munster V.J.
      Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions.
      make it difficult to ignore contaminated environmental surfaces as a potential etiology of hospital outbreaks.
      The rate of detecting MERS-CoV in our environmental samples was low (1.3%) compared with recently published data (PCR positive = 20.3%; culture positive = 4.0%),
      • Bin S.Y.
      • Heo J.Y.
      • Song M.S.
      • Lee J.
      • Kim E.H.
      • Park S.J.
      • et al.
      Environmental contamination and viral shedding in MERS patients during MERS-CoV outbreak in South Korea.
      but the current methods for isolating viruses from the environmental surfaces are not optimal.
      • Julian T.R.
      • Tamayo F.J.
      • Leckie J.O.
      • Boehm A.B.
      Comparison of surface sampling methods for virus recovery from fomites.
      Based on reported methodologies, we used a polyester swab, 1/4 lactated ringer solution,
      • Julian T.R.
      • Tamayo F.J.
      • Leckie J.O.
      • Boehm A.B.
      Comparison of surface sampling methods for virus recovery from fomites.
      PBS
      • Julian T.R.
      • Tamayo F.J.
      • Leckie J.O.
      • Boehm A.B.
      Comparison of surface sampling methods for virus recovery from fomites.
      and viral transport media
      • Bin S.Y.
      • Heo J.Y.
      • Song M.S.
      • Lee J.
      • Kim E.H.
      • Park S.J.
      • et al.
      Environmental contamination and viral shedding in MERS patients during MERS-CoV outbreak in South Korea.
      because they seem to give the best yield for isolating viruses from fomites. However, we did screening at the tail-end of our outbreak when the patients' viral load might have been low and our infection control practices might have been optimal. Additionally, MERS patients were managed in our ICU since 2013 and were usually cohorted in 1 unit where the staff became very meticulous about PPE use and environmental cleaning. Moreover, fairly weak disinfectants, such as povidone iodine, have a rapid virucidal activity (reduction in virus titer by ≥4 log10) against MERS-CoV, with an exposure time of just 15 seconds.
      • Eggers M.
      • Eickmann M.
      • Zorn J.
      Rapid and effective virucidal activity of povidone-iodine products against middle east respiratory syndrome coronavirus (MERS-CoV) and modified vaccinia virus ankara (MVA).
      Further, Leclercq et al demonstrated that at relatively low temperatures of 56°C, only 25 minutes was needed to reduce the initial titer by 4 log10, while at 65°C virucidy dropped significantly to 1 minute.
      • Leclercq I.
      • Batejat C.
      • Burguiere A.M.
      • Manuguerra J.C.
      Heat inactivation of the Middle East respiratory syndrome coronavirus.
      This sensitivity to weak disinfectants could explain why our stringent environmental cleaning policies may have attenuated the recovery of viral genetic material on fomites within the patients' rooms.

      Conclusions

      Our finding of MERS-CoV RNA on environmental samples within our ICU shows that the viral material may contaminate fomites and can be a theoretical cause of nosocomial infections. However, we did not use viral cultures; therefore, we do not know if the positive PCRs correlate with live viruses or infectivity. Despite this, we believe that in addition to proper hand hygiene and correct PPE donning and doffing, meticulous environmental cleaning is of paramount importance to eliminate health care outbreaks.

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