Middle East respiratory syndrome coronavirus infection other diagnostic studies
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]
Overview
Middle East Respiratory Syndrome (MERS) is a viral respiratory illness. It is caused by an emerging coronavirus, specifically a betacoronavirus called MERS-CoV (Middle East Respiratory Syndrome Coronavirus), first discovered in 2012. Being a relatively novel virus, there is no virus-specific prevention or treatment options for MERS patients. Attending to the fact that a vaccine hasn't been developed yet, enhancing infection prevention and control measures is critical to prevent the possible spread of MERS-CoV in hospitals and communities. Persons with symptoms suspicious of MERS-CoV infection need medical evaluation. According to the CDC: a certified case of MERS-CoV infection is considered an individual who shows laboratory confirmation of infection by MERS-CoV. This last one is given by a positive PCR test of ≥2 specific genomic targets or, a single positive target followed by successful sequencing of a second; while a probable case of MERS-CoV infection is an individual who has missing or inconclusive laboratory test results for the infection and that has been in close contact with another individual who is a "laboratory-confirmed case" of MERS-CoV infection. Laboratory tests, such as the PCR for MERS-CoV are available at state health departments, CDC and some international laboratories. Otherwise, MERS-CoV tests are not routinely available, despite the existence of a limited number of non-FDA-approved commercial tests.[1][2][3]
Other Diagnostic Studies
According to CDC guidelines:[4]
- Investigations of MERS-CoV and other respiratory pathogens may now be conducted simultaneously and additionally, positive results for another respiratory pathogen should not hinder testing for MERS-CoV.
- Health-care providers in the United States should continue to evaluate patients for MERS-CoV infection if they develop fever and pneumonia or acute respiratory distress syndrome within 14 days after traveling from countries in or near the Arabian Peninsula.
- Providers should also evaluate patients for MERS-CoV infection, in the presence of ARDS, fever or pneumonia and if they have been in close contact with recent travelers from the Arabian Peninsula who have fever and acute respiratory illness.
- Clusters of patients with severe acute respiratory illness, such as fever and pneumonia that requires hospitalization, must be evaluated for common respiratory pathogens and reported to local and state public health departments. In case a diagnosis isn't reached, particularly if the cluster includes health-care providers, testing for MERS-CoV should be considered, in consultation with state and local health departments. In this situation, all patients should be tested, even if they haven't had travel-related exposure.
- If symptoms have started more than 14 days prior, CDC guidelines recommend additional testing of a serum specimen via the CDC MERS-CoV serologic assay
- Laboratory confirmation of infection by MERS-CoV now requires a positive PCR test of ≥2 specific genomic targets or, a single positive target followed by successful sequencing of a second.
- Laboratory tests, such as the PCR for MERS-CoV are available at state health departments, CDC and some international laboratories. Otherwise, MERS-CoV tests are not routinely available, despite the existence of a limited number of non-FDA-approved commercial tests.
Polymerase Chain Reaction
According to the cases studied until now, reverse transcriptase polymerase chain reaction testing of specimens from the lower respiratory tract, such as tracheal aspirates or bronchoalveolar lavage, detain the highest sensitivity for the detection of MERS-CoV. However, upper respiratory tract specimens are still useful for diagnosis, particularly in mild cases, when a lower tract specimen cannot be obtained. [5][6][2][7][8][9][10] For the routine detection of MERS-CoV, three rRT-PCR assays have been developed.[11] These tests target different regions of the viral genome, namely:
- Region upstream of the E protein gene- upE
- Open reading frame 1a - ORF 1a
- Open reading frame 1b - ORF 1b
In some cases, when there is a need for confirmation of the results, sequencing is indicated.[5][12]
Serology
In order to identify MERS-CoV antibodies, different serology assays have been developed for this pathogen, namely:[13][14][15][16][17]
For these assays, the CDC has developed an approach with two steps:[18]
- Screening with ELISA
- Confirmation with indirect immunofluorescence or microneutralization test
Every sample should first be screened with ELISA and in case of a positive result, then this should be confirmed with a neutralization assay. Unfortunately, the data concerning sensitivity and specificity of these tests using antibodies for the detection of MERS-CoV, is very limited. According to the WHO, if a patient has a positive serologic test, but no PCR or sequencing test, then that individual is considered a probable case, considering that he meets the remaining criteria for this category.
References
- ↑ Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J; et al. (2014). "Repurposing of clinically developed drugs for treatment of Middle East Respiratory Coronavirus Infection". Antimicrob Agents Chemother. doi:10.1128/AAC.03036-14. PMID 24841273.
- ↑ 2.0 2.1 "Clinical management of severe acute respiratory infections when novel coronavirus is suspected: What to do and what not to do" (PDF).
- ↑ "MERS Prevention and Treatment".
- ↑ "Updated Information on the Epidemiology of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Guidance for the Public, Clinicians, and Public Health Authorities, 2012–2013".
- ↑ 5.0 5.1 Corman VM, Eckerle I, Bleicker T, Zaki A, Landt O, Eschbach-Bludau M; et al. (2012). "Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction". Euro Surveill. 17 (39). PMID 23041020.
- ↑ Memish ZA, Zumla AI, Al-Hakeem RF, Al-Rabeeah AA, Stephens GM (2013). "Family cluster of Middle East respiratory syndrome coronavirus infections". N Engl J Med. 368 (26): 2487–94. doi:10.1056/NEJMoa1303729. PMID 23718156.
- ↑ Drosten, Christian; Seilmaier, Michael; Corman, Victor M; Hartmann, Wulf; Scheible, Gregor; Sack, Stefan; Guggemos, Wolfgang; Kallies, Rene; Muth, Doreen; Junglen, Sandra; Müller, Marcel A; Haas, Walter; Guberina, Hana; Röhnisch, Tim; Schmid-Wendtner, Monika; Aldabbagh, Souhaib; Dittmer, Ulf; Gold, Hermann; Graf, Petra; Bonin, Frank; Rambaut, Andrew; Wendtner, Clemens-Martin (2013). "Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection". The Lancet Infectious Diseases. 13 (9): 745–751. doi:10.1016/S1473-3099(13)70154-3. ISSN 1473-3099.
- ↑ Guery, Benoit; Poissy, Julien; el Mansouf, Loubna; Séjourné, Caroline; Ettahar, Nicolas; Lemaire, Xavier; Vuotto, Fanny; Goffard, Anne; Behillil, Sylvie; Enouf, Vincent; Caro, Valérie; Mailles, Alexandra; Che, Didier; Manuguerra, Jean-Claude; Mathieu, Daniel; Fontanet, Arnaud; van der Werf, Sylvie (2013). "Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission". The Lancet. 381 (9885): 2265–2272. doi:10.1016/S0140-6736(13)60982-4. ISSN 0140-6736.
- ↑ Memish, Z. A.; Al-Tawfiq, J. A.; Makhdoom, H. Q.; Assiri, A.; Alhakeem, R. F.; Albarrak, A.; Alsubaie, S.; Al-Rabeeah, A. A.; Hajomar, W. H.; Hussain, R.; Kheyami, A. M.; Almutairi, A.; Azhar, E. I.; Drosten, C.; Watson, S. J.; Kellam, P.; Cotten, M.; Zumla, A. (2014). "Respiratory Tract Samples, Viral Load and Genome Fraction Yield in patients with Middle East Respiratory Syndrome". Journal of Infectious Diseases. doi:10.1093/infdis/jiu292. ISSN 0022-1899.
- ↑ Assiri, Abdullah; Al-Tawfiq, Jaffar A; Al-Rabeeah, Abdullah A; Al-Rabiah, Fahad A; Al-Hajjar, Sami; Al-Barrak, Ali; Flemban, Hesham; Al-Nassir, Wafa N; Balkhy, Hanan H; Al-Hakeem, Rafat F; Makhdoom, Hatem Q; Zumla, Alimuddin I; Memish, Ziad A (2013). "Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study". The Lancet Infectious Diseases. 13 (9): 752–761. doi:10.1016/S1473-3099(13)70204-4. ISSN 1473-3099.
- ↑ "Laboratory Testing for Middle East Respiratory Syndrome Coronavirus" (PDF).
- ↑ Corman VM, Müller MA, Costabel U, Timm J, Binger T, Meyer B; et al. (2012). "Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections". Euro Surveill. 17 (49). PMID 23231891.
- ↑ name=WHO5>"Laboratory Testing for Middle East Respiratory Syndrome Coronavirus" (PDF).
- ↑ team, European Centre for Disease Prevention and Control (ECDC)-Health Comunication Unit- Eurosurveillance editorial. “Assays for Laboratory Confirmation of Novel Human Coronavirus (hCoV-EMC) Infections.” Text, June 12, 2012. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20334.
- ↑ Chan, Kwok-Hung, Jasper Fuk-Woo Chan, Herman Tse, Honglin Chen, Candy Choi-Yi Lau, Jian-Piao Cai, Alan Ka-Lun Tsang, et al. “Cross-Reactive Antibodies in Convalescent SARS Patients’ Sera against the Emerging Novel Human Coronavirus EMC (2012) by Both Immunofluorescent and Neutralizing Antibody Tests.” The Journal of Infection 67, no. 2 (August 2013): 130–40. doi:10.1016/j.jinf.2013.03.015.
- ↑ Buchholz, U, M A Müller, A Nitsche, A Sanewski, N Wevering, T Bauer-Balci, F Bonin, et al. “Contact Investigation of a Case of Human Novel Coronavirus Infection Treated in a German Hospital, October-November 2012.” Euro Surveillance: Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin 18, no. 8 (2013).
- ↑ Reusken, C, H Mou, G J Godeke, L van der Hoek, B Meyer, M A Müller, B Haagmans, et al. “Specific Serology for Emerging Human Coronaviruses by Protein Microarray.” Euro Surveillance: Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin 18, no. 14 (2013): 20441.
- ↑ name=WHO5>"Laboratory Testing for Middle East Respiratory Syndrome Coronavirus" (PDF).