Risk Factors for Middle East Respiratory Syndrome Coronavirus Infection Among Healthcare Personnel

Basem M. Alraddadi; Hanadi S. Al-Salmi; Kara Jacobs-Slifka; Rachel B. Slayton; Concepcion F. Estivariz; Andrew I. Geller; Hanan H. Al-Turkistani; Sanaa S. Al-Rehily; Haleema A. Alserehi; Ghassan Y. Wali; Abeer N. Alshukairi; Esam I. Azhar; Lia Haynes; David L. Swerdlow; John A. Jernigan; Tariq A. Madani

Disclosures

Emerging Infectious Diseases. 2016;22(11):1915-1920. 

In This Article

Discussion

We report this seroepidemiologic study to quantify the risk for MERS-CoV infection among HCP. The findings have important implications for infection control practice. Our results suggest that the attack rate of MERS-CoV infection among healthcare workers is substantially higher than that in previous reports that used nonserologic methods of detection.[15–17] The spectrum of illness appears to be broader than previously described; infection caused a relatively mild illness in most cases. Infections occurred almost exclusively among HCP having close contact with a MERS-CoV patient.

Most HCP in this cohort reported always covering their nose and mouth with a medical mask or N95 respirator when caring for a MERS-CoV patient, which appeared to protect against infection among HCP participating in aerosol-generating procedures. When we stratified by type of mask, we observed an increased risk for MERS-CoV infection among HCP who reported always using medical masks and, conversely, a lower risk among those who reported always using N95 respirators. Taken together, these results raise the hypothesis that short-range aerosol transmission might have factored in transmission. Previous studies suggest that some respiratory viruses (e.g., influenza, severe acute respiratory syndrome coronavirus, rhinovirus) that are transmitted primarily by droplets and/or contact might simultaneously be spread through aerosol under certain conditions and perhaps by certain patients.[18–22] Aerosol transmission in close proximity to the patient might not necessarily be accompanied by long-range transmission because the risk for such transmission might be affected by the infectious dose, the amount of aerosolized particles generated at the source, and the rate of biologic decay of the agent.[22] We found no evidence of long-range aerosol transmission. Until additional information about the mode of MERS-CoV transmission is available, it seems prudent to take precautions against aerosol spread in healthcare settings when feasible to do so.

The combined attack rate for HCP who worked in units known to house patients with MERS-CoV infection (8%) was substantially higher than that in previous studies, which described attack rates for HCP of ≤1%.[15–17] These prior studies did not use serologic methods to detect infection but rather relied on rRT-PCR of nasopharyngeal swabs. All 20 seropositive HCP in our study were screened with nasopharyngeal swabs, and only 5 (25%) of these tests showed evidence of MERS-CoV by rRT-PCR. Therefore, screening for viral shedding using nasopharyngeal swabs might be an insensitive method for detecting infection, perhaps because of variability in timing of samples in relationship to exposure, and studies relying solely on this method of case detection might underestimate attack rates.

Our study suggests that almost all MERS-CoV infection among HCP occurs among those having close contact with patients known to be infected with MERS-CoV. We observed the highest attack rates among radiology technicians, followed by nurses. We hypothesize that radiology technicians most likely were exposed while obtaining portable chest radiographs, a procedure that requires close contact (e.g., positioning the patient for cassette placement) with patients who might be likely to have worsening respiratory status and be highly contagious. We identified no seropositive HCP who worked in the unit not known to house any MERS-CoV patients, suggesting that the background rate of MERS-CoV infection among HCP was low in the absence of known exposure to infected patients and that the virus was not circulating widely among staff.

HCP who had undergone infection control training specific to MERS-CoV had a lower risk for infection. This finding underscores the critical need for adequate infection control training, especially in settings with ongoing transmission of epidemiologically important pathogens.

We observed a broad spectrum of illness among HCP, and in most cases illness was relatively mild. Most illnesses were characterized by myalgia, fever, headache, and dry cough. Gastrointestinal symptoms were present in 50% of infected HCP; and 3 (15%) reported no symptoms. Most seropositive HCP with symptoms sought care, but only a small minority were recognized as having MERS-CoV infection. All 20 infected HCP survived, and only 5 required hospitalization. The spectrum of illness we observed was broader than that described in previous case series of MERS-CoV infection,[15,23,24] which probably were biased toward identifying patients with more severe illness because testing for MERS-CoV infection has largely been triggered by case definitions requiring evidence of pneumonia.[10] The observation that most MERS-CoV infections among HCP are likely to be relatively mild and unrecognized has potentially important implications for infection control practice. Although little is known about risk for transmission from persons with mild MERS-CoV-infection, HCP with unrecognized MERS-CoV infection might be a reservoir for transmission to hospitalized patients who are more susceptible to severe illness because of underlying illnesses. Transmission from persons with unrecognized MERS-CoV infections might have contributed to the major role healthcare-associated transmission has played in the epidemiology of MERS-CoV.[6,8,9] Thus, control of transmission in healthcare settings might depend on maintaining a low threshold for suspicion of MERS-CoV infection among exposed HCP and other persons with a relatively mild viral syndrome.

Our study did not identify strong associations with underlying chronic illnesses, most likely because the prevalence of such conditions was low (<10%) in this population. HCPs with a history of smoking had a risk for infection almost 3 times that of nonsmokers. We found no association between MERS-CoV infection and sex. Most case series to date have demonstrated a male predominance among case-patients,[15,23,24] but our study suggests this association might be explained by social and behavioral factors that increase exposure to MERS-CoV, rather than a sex-specific difference in biological susceptibility.

Our study has several strengths. We compared MERS-CoV infected and uninfected HCP to determine risk factors for acquiring infection during patient care. The use of serologic testing to determine infection status enabled unbiased case ascertainment, an examination of the full spectrum of disease, and a comparison of the risks associated with a wide range of specific patient care activities.

Our study also has limitations. First, questionnaires were administered several weeks after possible exposures, and therefore the potential exists for recall bias. Recall bias can limit assessment of important variables, such as frequency of exposure and duration of contact during specific procedure. However, HCP and interviewers were unaware of their serologic status at the time of interview; their answers would not have been influenced by knowledge of these results. Moreover, symptoms of illness were unlikely to have introduced systematic bias to responses because most uninfected and infected groups reported illness. Second, we used only 1 serum sample for serologic testing. Because of the retrospective nature of our study, baseline serologic tests were not conducted, and therefore the potential exists for false-positive results. However, seroprevalence of MERS-CoV antibodies in Saudi Arabia is low (0.15%), making misclassification bias unlikely.[25] Third, infected asymptomatic HCP could serve as a potential source of infection to other HCP. Given the retrospective nature of our study, we were not able to characterize these potential exposures. Fourth, as is common with early studies of emerging infectious diseases, sufficiently powering studies can be difficult. Whether negative findings were true null findings or due to small sample sizes is unclear.

In conclusion, we report results of a seroepidemiologic study to quantify risk for MERS-CoV infection among HCP. The attack rate appears to be substantially higher than that in prior reports that used nonserologic methods of detection. Infection in this population most often results in mild illness that might be overlooked; programs to identify and exclude ill HCP who have been exposed to patients with MERS-CoV might help eliminate this reservoir for transmission. Our findings also suggest N95 respirators might be more protective against MERS-CoV infection while in close contact with an infected patient and highlight the possible role of short-range aerosol transmission of MERS-CoV in healthcare settings. Education about standard and MERS-CoV infection control practices appears to be protective, suggesting that adherence to basic practices can effectively prevent MERS-CoV infection among HCP.

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