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SARS-CoV-2 Enfeksiyonunun Mikrobiyolojik Tanısı

Year 2021, Volume: 28 Issue: COVİD-19 ÖZEL SAYI, 137 - 145, 01.05.2021
https://doi.org/10.17343/sdutfd.906925

Abstract

Aralık 2019’da Çin’den başlayarak çok kısa bir süre içerisinde tüm dünyayı etkisi altına alan Coronavirus Disease 2019 (COVID-19) pandemisi, bugüne kadar görülen en ciddi küresel sağlık sorunlarından biri haline gelmiştir. Bu süreçte, zamanında ve doğru uygulanan mikrobiyolojik tanı testleri, salgının ve vaka yönetiminin önemli bir parçası olmuştur. Pandeminin başlangıcından itibaren solunum yolu örneklerinde severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA’sını saptamaya yönelik olarak geliştirilen gerçek zamanlı ters transkriptaz-polimeraz zincir reaksiyonu (RT-PCR), en yaygın kullanılan tanı yöntemidir. RT-PCR ile virüs RNA’sının gösterilmesi COVID-19 hastalığının kesin tanısını sağlamakla birlikte negatif test sonucu enfeksiyon olasılığını dışlamaz. Klinik şüpheli olgularda 24-48 saat arayla tekrarlayan örneklerin alınması ve ciddi akciğer bulguları olan hastalarda tanı için alt solunum yolu örneklerinin tercih edilmesi gereklidir. Düşük maliyetli, uygulanması kolay ve hızlı sonuç alınabilen antijen testlerinin kullanımı, viral yükün yüksek olduğu hastalığın akut evresi ile sınırlıdır. Duyarlılık ve özgüllük sorunlarından dolayı antijen testleriyle elde edilen sonuçların RT-PCR testleri ile doğrulanması gerekir. Antikor testleri, virüs ile karşılaşılmış olduğunu gösterir. Hastaların virüse karşı antikor yanıtının değişken ve geç olması nedeniyle antikor testleri, akut dönemde hastalığın tanısında tek başına kullanılmamalıdır. Semptomların başlangıcından 2-3 hafta sonra alınan kan örneklerinde çalışılan antikor testleri moleküler tanıya yardımcı ek test olarak kullanılabilir. Bu derlemede, günümüze kadar elde edilen veriler doğrultusunda SARS-CoV-2 enfeksiyonunun mikrobiyolojik tanısında kullanılan yöntemlerin özellikleri, klinik açıdan sağladıkları avantajlar ve kısıtlı yönleri tartışılmıştır.

References

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  • Hanson KE, Caliendo AM, Arias CA, Englund JA, Hayden MK, Lee MJ, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing. Clin Infect Dis 2020 12;ciaa1343.
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  • Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 2020;323:1843-4.
  • To KKW, Tsang OTY, Leung WS, Tam AR, Wu TC, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis 2020;20:565-74.
  • Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020;581:465-9.
  • Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect 2020;9:386-9.
  • Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 2020;26:845-8.
  • Chen M, Qin R, Jiang M, Yang Z, Wen W, Li J. Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review. Int J Infect Dis 2021;104:415-22.
  • Qu J, Wu C, Li X, Zhang G, Jiang Z, Li X. Profile of Immunoglobulin G and IgM Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020;71:2255-8.
  • World Health Organization, Infection prevention and control during health care when COVID-19 is suspected, Interim guidance [Internet]. 19 March 2020 [Cited 30 March 2021] Available from: https://www.who.int/publications/i/item/10665-331495.
  • Tang YW, Schmitz JE, Persing DH, Stratton CW. Laboratory Diagnosis of COVID-19: Current Issues and Challenges. J Clin Microbiol 2020;58:e00512-20.
  • Jayamohan H, Lambert CJ, Sant HJ, Jafek A, Patel D, Feng H. SARS-CoV-2 pandemic: a review of molecular diagnostic tools including sample collection and commercial response with associated advantages and limitations. Anal Bioanal Chem 2021;413:49-71.
  • Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Ann Intern Med 2020;173:262-7.
  • Patel R, Babady E, Theel ES, Storch GA, Pinsky BA, George KS, et al. Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS-CoV-2/COVID-19. mBio 2020;11:e00722-20.
  • Surkova E, Nikolayevskyy V, Drobniewski F. False-positive COVID-19 results: hidden problems and costs. Lancet Respir Med 2020;8:1167-8.
  • Huang WE, Lim B, Hsu CC, Xiong D, Wu W, Yu Y, et al. RT-LAMP for rapid diagnosis of coronavirus SARS-CoV-2. Microb Biotechnol 2020;13:950-61.
  • Broughton JP, Deng X, Yu G, Fasching CL, Servellita V, Singh J, et al. CRISPR-Cas12-based detection of SARS-CoV-2. Nat Biotechnol 2020;38:870-4.
  • Peeling RW, Olliaro PL, Boeras DI, Fongwen N. Scaling up COVID-19 rapid antigen tests: promises and challenges. Lancet Infect Dis 2021; (published online Feb 23).
  • World Health Organization, SARS-CoV-2 antigen-detecting rapid diagnostic tests: an implementation guide [Internet]. 21 December 2020 [Cited 30 March 2021] Available from: https://www.who.int/publications/i/item/9789240017740.
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  • COVID-19 Mikrobiyolojik Tanı Testlerinin Pandemide Akılcı Kullanımı [Internet]. Ocak 2021 [Cited 30 March 2021] Available from: https://www.klimudkoronavirus.org/wp-content/uploads/2021/02/COVID-19-MİKROBİYOLOJİK-TANI-TESTLERİNİN-PANDEMİDE-AKILCI-KULLANIMI-Klinisyen-2.pdf
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  • Okba NMA, Müller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, et al. Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients. Emerg Infect Dis 2020;26:1478-88.
  • Zhong L, Chuan J, Gong B, Shuai P, Zhou Y, Zhang Y, et al. Detection of serum IgM and IgG for COVID-19 diagnosis. Sci China Life Sci 2020;63:777-80.
  • Coste AT, Jaton K, Papadimitriou-Olivgeris M, Greub G, Croxatto A. Comparison of SARS-CoV-2 serological tests with different antigen targets. J Clin Virol 2021;134:104690.
  • Kohmer N, Westhaus S, Rühl C, Ciesek S, Rabenau HF. Clinical performance of different SARS‐CoV‐2 IgG antibody tests. J Med Virol 2020;92:2243-7.
  • Pan Y, Li X, Yang G, Fan J, Tang Y, Zhao J, et al. Serological immunochromatographic approach in diagnosis with SARS-CoV-2 infected COVID-19 patients. J Infect 2020;81:e28-e32.
  • Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, et al. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J Med Virol 2020;92:1518-24.

Microbiological Diagnosis of SARS-CoV-2 Infection

Year 2021, Volume: 28 Issue: COVİD-19 ÖZEL SAYI, 137 - 145, 01.05.2021
https://doi.org/10.17343/sdutfd.906925

Abstract

The Coronavirus Disease 2019 (COVID-19) pandemic, which began in China in December 2019 and affected the whole world in a very short time, has become one of the most serious global health problems to date. In this process, timely and correctly applied microbiological diagnostic tests have been an important part of the epidemic and case management. Since the beginning of the pandemic, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), which has been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory tract samples, is the most widely used diagnostic method. The detection of the virus RNA by RT-PCR provides the definitive diagnosis of COVID-19 disease, but a negative test result does not exclude the possibility of infection. In clinically suspicious cases, repeated samples should be taken within 24-48 hours and lower respiratory tract samples should be preferred for diagnosis in patients with severe lung findings. The use of low-cost and easy-to-apply rapid antigen tests is limited to the acute phase of the disease when viral load is high. Due to sensitivity and specificity problems, the antigen test results should be confirmed by RT-PCR tests. Antibody tests indicate the exposure to the virus. Antibody tests should not be used alone in the diagnosis of the disease in acute phase, because the antibody response of the patients against the virus is variable and late. Antibody tests, which are performed on the blood samples taken 2-3 weeks after the onset of symptoms, can be used as an additional test to aid molecular diagnosis. In this review, the features, clinical advantages and limitations of the methods used in the microbiological diagnosis of SARS-CoV-2 infection are discussed in line with the obtained data to date.

References

  • Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-3.
  • Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol 2020;5:536-44.
  • T.C. Sağlık Bakanlığı Halk Sağlığı Genel Müdürlüğü COVID-19 (SARS-CoV-2 Enfeksiyonu) Rehberi, Genel Bilgiler, Epidemiyoloji ve Tanı [Internet]. 7 Aralık 2020 [Cited 30 March 2021] Available from: https://covid19.saglik.gov.tr/Eklenti/39551/0/covid-19rehberigenelbilgilerepidemiyolojivetanipdf.pdf.
  • Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, et al. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol 2016;24:490-502.
  • Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nat Med 2020;26:450-2.
  • Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: Emergence, transmission, and characteristics of human coronaviruses. J Adv Res 2020;24:91-8.
  • Ortiz-Prado E, Simbana-Rivera K, Gomez-Barreno L, Rubio-Neira M, Guaman LP, Kyriakidis NC, et al. Clinical, molecular, and epidemiological characterization of the SARS-CoV-2 virus and the Coronavirus Disease 2019 (COVID-19), a comprehensive literature review. Diagn Microbiol Infect Dis 2020;98:115094.
  • Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020;395:565-74.
  • Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019;17:181-92.
  • Zhang YZ, Holmes EC. A Genomic Perspective on the Origin and Emergence of SARS-CoV-2. Cell 2020;181:223-7.
  • Chen Y, Liu Q, Gou D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J Med Virol 2020;92:418-23.
  • World Health Organization, Diagnostic testing for SARS-CoV-2: interim guidance. [Internet]. 11 September 2020 [Cited 30 March 2021] Available from: https://apps.who.int/iris/handle/10665/334254.
  • Hanson KE, Caliendo AM, Arias CA, Hayden MK, Englund JA, Lee MJ, et al. The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing. Clin Infect Dis 2021;22:ciab048.
  • Caruana G, Croxatto A, Coste AT, Opota O, Lamoth F, Jaton K, et al. Diagnostic strategies for SARS-CoV-2 infection and interpretation of microbiological results. Clin Microbiol Infect 2020;26:1178-82.
  • Hanson KE, Caliendo AM, Arias CA, Englund JA, Hayden MK, Lee MJ, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Serologic Testing. Clin Infect Dis 2020 12;ciaa1343.
  • Zou L, Ruan F, Huang M, Liang L, Huang H, Hong Z, et al. SARS-CoV-2 Viral Load in Upper Respiratory Specimens of Infected Patients. N Engl J Med 2020;382:1177-9.
  • Pan Y, Zhang D, Yang P, Poon LLM, Wang Q. Viral load of SARS-CoV-2 in clinical samples. Lancet Infect Dis 2020;20:411-2.
  • Sethuraman N, Jeremiah SS, Ryo A. Interpreting Diagnostic Tests for SARS-CoV-2. JAMA 2020;323:2249-51.
  • Erensoy S. COVID-19 Pandemisinde SARS-CoV-2 ve Mikrobiyolojik Tanı Dinamikleri. Mikrobiyol Bul 2020;54:497-509.
  • Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med 2020;382:1199-1207.
  • Yan Y, Chang L, Wang L. Laboratory testing of SARS-CoV, MERS-CoV, and SARS-CoV-2 (2019-nCoV): Current status, challenges, and countermeasures. Rev Med Virol 2020;30:e2106.
  • Zhao J, Yuan Q, Wang H, Liu W, Liao X, Su Y, et al. Antibody Responses to SARS-CoV-2 in Patients With Novel Coronavirus Disease 2019. Clin Infect Dis 2020;71:2027-34.
  • Loeffelholz MJ, Tang YW. Laboratory diagnosis of emerging human coronavirus infections - the state of the art. Emerg Microbes Infect 2020;9:747-56.
  • Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 2020;323:1843-4.
  • To KKW, Tsang OTY, Leung WS, Tam AR, Wu TC, Lung DC, et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis 2020;20:565-74.
  • Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020;581:465-9.
  • Zhang W, Du RH, Li B, Zheng XS, Yang XL, Hu B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerg Microbes Infect 2020;9:386-9.
  • Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med 2020;26:845-8.
  • Chen M, Qin R, Jiang M, Yang Z, Wen W, Li J. Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review. Int J Infect Dis 2021;104:415-22.
  • Qu J, Wu C, Li X, Zhang G, Jiang Z, Li X. Profile of Immunoglobulin G and IgM Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020;71:2255-8.
  • World Health Organization, Infection prevention and control during health care when COVID-19 is suspected, Interim guidance [Internet]. 19 March 2020 [Cited 30 March 2021] Available from: https://www.who.int/publications/i/item/10665-331495.
  • Tang YW, Schmitz JE, Persing DH, Stratton CW. Laboratory Diagnosis of COVID-19: Current Issues and Challenges. J Clin Microbiol 2020;58:e00512-20.
  • Jayamohan H, Lambert CJ, Sant HJ, Jafek A, Patel D, Feng H. SARS-CoV-2 pandemic: a review of molecular diagnostic tools including sample collection and commercial response with associated advantages and limitations. Anal Bioanal Chem 2021;413:49-71.
  • Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Ann Intern Med 2020;173:262-7.
  • Patel R, Babady E, Theel ES, Storch GA, Pinsky BA, George KS, et al. Report from the American Society for Microbiology COVID-19 International Summit, 23 March 2020: Value of Diagnostic Testing for SARS-CoV-2/COVID-19. mBio 2020;11:e00722-20.
  • Surkova E, Nikolayevskyy V, Drobniewski F. False-positive COVID-19 results: hidden problems and costs. Lancet Respir Med 2020;8:1167-8.
  • Huang WE, Lim B, Hsu CC, Xiong D, Wu W, Yu Y, et al. RT-LAMP for rapid diagnosis of coronavirus SARS-CoV-2. Microb Biotechnol 2020;13:950-61.
  • Broughton JP, Deng X, Yu G, Fasching CL, Servellita V, Singh J, et al. CRISPR-Cas12-based detection of SARS-CoV-2. Nat Biotechnol 2020;38:870-4.
  • Peeling RW, Olliaro PL, Boeras DI, Fongwen N. Scaling up COVID-19 rapid antigen tests: promises and challenges. Lancet Infect Dis 2021; (published online Feb 23).
  • World Health Organization, SARS-CoV-2 antigen-detecting rapid diagnostic tests: an implementation guide [Internet]. 21 December 2020 [Cited 30 March 2021] Available from: https://www.who.int/publications/i/item/9789240017740.
  • Diao B, Wen K, Chen J, Liu Y, Yuan Z, Han C, et al. Diagnosis of Acute Respiratory Syndrome Coronavirus 2 Infection by Detection of Nucleocapsid Protein. medRxiv 2020; DOI: 10.1101/2020.03.07.20032524.
  • COVID-19 Mikrobiyolojik Tanı Testlerinin Pandemide Akılcı Kullanımı [Internet]. Ocak 2021 [Cited 30 March 2021] Available from: https://www.klimudkoronavirus.org/wp-content/uploads/2021/02/COVID-19-MİKROBİYOLOJİK-TANI-TESTLERİNİN-PANDEMİDE-AKILCI-KULLANIMI-Klinisyen-2.pdf
  • Azkur AK, Akdis M, Azkur D, Sokolowska M, van de Veen W, Brüggen MC, et al. Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19. Allergy 2020;75:1564-81.
  • Okba NMA, Müller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, et al. Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients. Emerg Infect Dis 2020;26:1478-88.
  • Zhong L, Chuan J, Gong B, Shuai P, Zhou Y, Zhang Y, et al. Detection of serum IgM and IgG for COVID-19 diagnosis. Sci China Life Sci 2020;63:777-80.
  • Coste AT, Jaton K, Papadimitriou-Olivgeris M, Greub G, Croxatto A. Comparison of SARS-CoV-2 serological tests with different antigen targets. J Clin Virol 2021;134:104690.
  • Kohmer N, Westhaus S, Rühl C, Ciesek S, Rabenau HF. Clinical performance of different SARS‐CoV‐2 IgG antibody tests. J Med Virol 2020;92:2243-7.
  • Pan Y, Li X, Yang G, Fan J, Tang Y, Zhao J, et al. Serological immunochromatographic approach in diagnosis with SARS-CoV-2 infected COVID-19 patients. J Infect 2020;81:e28-e32.
  • Li Z, Yi Y, Luo X, Xiong N, Liu Y, Li S, et al. Development and clinical application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection diagnosis. J Med Virol 2020;92:1518-24.
There are 49 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Reviews
Authors

Mümtaz Cem Şirin 0000-0002-7349-3438

Emel Sesli Çetin 0000-0001-5231-3824

Buket Arıdoğan 0000-0003-0980-2205

Publication Date May 1, 2021
Submission Date April 3, 2021
Acceptance Date April 10, 2021
Published in Issue Year 2021 Volume: 28 Issue: COVİD-19 ÖZEL SAYI

Cite

Vancouver Şirin MC, Sesli Çetin E, Arıdoğan B. SARS-CoV-2 Enfeksiyonunun Mikrobiyolojik Tanısı. Med J SDU. 2021;28(COVİD-19 ÖZEL SAYI):137-45.

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