Increasing Role of Medical Biochemistry During COVID - 19 Pandemic

.: PREFACE
ÖN SÖZ
PREFACE
Prof. Dr. Doğan YÜCEL
Lokman Hekim Üniversitesi Tıp Fakültesi, Tıbbi Biyokimya ABD, Ankara, Türkiye
Article Language: TR
İnsanlık hızla yayılan bir pandemiyle karşı karşıya. Ağır akut respiratuvar koronavirüs-2 sendromu (SARS-CoV-2) pandemisi, insanlığın 100 yıldan beri karşı karşıya kaldığı en ciddi halk sağlığı sorunu. Pandemi sırasında laboratuvar tıbbının önemi daha bir gün yüzüne çıktı. Klinik laboratuvarcılar ve bilimciler, SARS-CoV-2 pandemisine karşı kritik bir görev üstlendiler. İlkin, laboratuvar bilimcileri tarafından virüsün genetik yapısı ve vücutta doku ve hücrelerle etkileşimi belirlendi.Ardından, virüsü saptamaya yönelik testler ve hastalığın biyokimyasal takibine ve hastalarda virüse karşı oluşan serolojik antikor cevabına yönelik testler, hep laboratuvarcılar tarafından gerçekleştirildi. Günümüzde SARS-CoV-2 enfeksiyonunun hızlı tanısı, COVID-19'lu hastaların serolojik takibi, hastanede tedavi gören ağır hastaların biyokimyasal takibi ya da COVID-19'un epidemiyolojik sürveyansı, tümüyle tıbbi laboratuvar hizmetine gerek duyuyor. Günümüzde eksikliklerine rağmen nükleik asit amplifikasyon testleri (NAAT), otoriteler tarafından enfeksiyonun akut fazında tanı için 'altın standardı' olarak kabul edilmektedir. Ve NAAT'lerin temeli 1985'de bir biyokimyacı olan Kary Mullis'in geliştirdiği polimeraz zincir reaksiyonuna (PCR) dayanmaktadır. Gene biyokimyacılar tarafından geliştirilen multipleks gerçek zamanlı PCR, izotermal nükleik asit amplifikasyonu, RNA hedefli ''clustered regularly interspaced short palindromic repeats'' (CRISPR) gibi tekniklere dayanan testler SARS-CoV-2 tanısında kullanılmaktadır. Moleküler testlerden sonra, enfeksiyonun akut döneminde antijen testleri de gittikçe daha çok kullanılır hâle gelmektedir. Ek olarak, antikor testleri; COVID-19 hastalarının enfeksiyon sonrasında, nispeten enfeksiyonun daha sonraki dönemlerinde patojene karşı geliştirdiği immün cevabı değerlendirmek için kullanılmaktadır. Serolojik çalışmalar aynı zamanda aşıya karşı gelişen immün cevabın belirlenmesi ve aşı etkinliğinin değerlendirilmesi açısından da esastır.

Öte yandan, konvansiyonel biyokimyasal testlerin önemi küçümsenmemelidir. Konvansiyonel biyokimyasal testler klinisyenlerin karar sürecinde ve hastaların tanı ve takibinde, özellikle de yoğun bakım birimlerinde, hastalığın şiddetinin belirlenmesinde, prognozun saptanmasında, komplikasyonların ve tedaviye cevabın değerlendirilmesinde esastır. Aşağıdaki testler COVID19 hastalarının hastane döneminde yoğun bir şekilde kullanılmaktadır: Tanı için nötrofil, lenfosit ve eozinofil sayımı, C-reaktif protein (CRP), laktat dehidrogenaz (LDH), aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), üre, kreatinin, prokalsitonin (PCT) ve fibrinojen; hastalık şiddetinin belirlenmesinde lenfosit sayımı, LDH, kreatin kinaz MB izoenzimi, kardiyak troponinler, brain natriüretik peptit (BNP) veya NT-proBNP, D-dimer, fibrinojen, CRP, PCT, LDH, protrombin zamanı (PT) ve aktive protrombin zamanı (APTT); prognoz için D-dimer yüksekliği, trombosit düşüklüğü, beyin omurilik sıvısında (BOS) interlökin 6 (IL-6), BOS'ta IL-8 ile birlikte IL-8, tümör nekroz faktör α (TNFα) ve β2-mikroglobulin; tedaviye cevabın izlenmesi için LDH, CK, CRP, AST ve ALT'nin azalışı; komplikasyonlar için PCT, CRP, ferritin, D-dimer, IL-2, IL-7, TNFα, fibrinojen, APTT ve PT'de azalma.

Bu parametreler uygulamada aşırı kullanılmakta olup klinik laboratuvarlarda bazı stok ve tedarik sorunlarının yaşanmasına yol açmıştır.

Pandemi sırasında diğer bir önemli konu personelin bu çok bulaşıcı virüs nedeniyle hastalanmasını önlemeye yönelik önlemler almaktır. Bu amaçla kılavuzlar hazırlanmış ve laboratuvar uzmanlarıyla ve ortamıyla paylaşılmıştır.

Tüm eğitim ve öğretim birimlerinde tıbbi biyokimya asistanlarının eğitimi ve öğretimi de vazgeçilemez bir görevdi. Bu yüzden dijital ortamda uzaktan eğitim tekniklerini kullanarak çok sayıda seminer, kurs ve konferans yapıldı. Zaten uzaktan eğitim tekniklerini öğrenmek zorundaydık ve pandemi bizleri bu yeni gelişmekte olan uzaktan eğitim yollarını öğrenmeye itti. Bu kitapta, ciddi bir genel halk sağlığı sorununa tıbbi biyokimyanın katkısı ve yeni gelişmekte olan eğitim ve öğretim imkânları, her biri kendi alanında yetkin meslektaşlarımız tarafından tüm boyutlarıyla ele alındı.

Sonuç olarak, COVID-19 pandemisinin genel olarak tıbbın, özel olarak laboratuvar tıbbının önemini öne çıkardığı kuşku götürmez (Umuyorum, Türkiye'de merkezi otorite Sağlık Bakanlığı da bu gerçeği görür ve laboratuvar uzmanları ile çalışanlarının özlük haklarını iade eder). Gene de, şartlar ne olursa olsun, tıbbi laboratuvar çalışanları SARS-CoV-2 enfeksiyonunun tarama, tanı, takip ve tedavisinde yaşamsal rol oynamaya devam edecektir.

Sonuçta laboratuvar bilimcilerinin, diğer tıp mesleklerinin çalışanları, sanayi ve kamu sağlık otoritesiyle birlikte pandeminin üstesinden geleceğine inanıyoruz.

Kitabın hazırlanmasında emeği geçen tüm arkadaşlarıma teşekkür ederim.
Türk Biyokimya Derneği'ne bu fırsatı veren Türkiye Klinikleri'ne teşekkür ederim.

Son olarak, bu kitabı COVID-19 nedeniyle yaşamını yitiren sağlık çalışanlarına ithaf ediyoruz.

Saygılarımla.

Prof. Dr. Doğan YÜCEL
Editör

KAYNAKLAR

1. Yilmaz E, Akyön Y, Serdar M. The molecular footprints of COVID-19. Turk J Biochem. 2020;45(3):241-8.
2. Saatçi E. Newly developed diagnostic methods for SARS-CoV-2 detection. Turk J Biochem.2020;45(5):465-74.
3. Adeli K. Critical role of laboratory medicine in the global response to the COVID-19 pandemic. Clin Chem Lab Med. 2020;58(7):1019- 20.
4. Lippi G, Horvath A, Adeli K. Editorial and executive Summary: IFCC Interim Guidelines on clinical laboratory testing during the COVID19 pandemic. Clin Chem Lab Med. 2020;58(12):1965-9.
5. Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated withCOVID-19 disease progression. Crit Rev Clin Lab Sci. 2020;57(6):389-99.
6. Tomo S, Karli S, Dharmalingam K, Yadav D, Sharma P. The clinical laboratory: a key player in diagnosis and management of COVID19. eJIFCC. 2020;31(4):326-46.
7. Yucel M, Avsar C. The effect of COVID-19 pandemic on biochemistry test consumption numbers and variety. Turk J Biochem. 2020;45(3):339-41.
8. Zengi O, Aykal G, Coskun C, Serdar M, Yucel D. COVID-19 laboratory biosafety guide. Turk J Biochem. 2020;45(3):461-3.
Humanity is in a rapidly spreading pandemic environment. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is the most serious public health trouble which humanity has been faced for a hundred years. During the pandemic, the importance of laboratory medicine has become more clear. Clinical laboratorians and scientists have taken on a critical role in the response to the SARS-CoV-2 pandemic. At first, the genetic structure and interaction of the virus with tissues or cells in the body were determined by laboratory scientists. Secondly, assays aiming to detect the virus and then biochemical monitoring of the disease as well as the determination of patients' antibody response against infection by serological assays were all developed by laboratorians. Currently, rapid diagnosis of SARS-CoV-2 infection, serological monitoring of the patients with COVID-19, biochemical monitoring of hospitalized patients who severely affected by SARS-CoV-2 or epidemiological surveillance of COVID-19 are all need laboratory medicine services. Despite their shortcomings, nucleic acid amplification testing (NAAT) is accepted as the 'golden standard' for diagnosis during the acute phase of the infection by the authorities today. And, their essential pivot is polymerase chain reaction (PCR) developed by a biochemist, Kary Mullis, in 1985. There have been other molecular assays developed by biochemists such as multiplexed real time - PCR, isothermal nucleic acid amplification, the RNA targeting clustered regularly interspaced short palindromic repeats based assays and they are used for SARS-CoV-2 detection. After molecular assays, antigen testing is becoming more and more common during the acute phase of infection. Additionally, antibody assays are used for the detection of the immune response of the patient with COVID-19 against pathogen during post-infection and relatively later period infection. Serologic studies are also essential for the determination of vaccine efficiency and for the evaluation of the immune response.

On the other hand, the importance of conventional biochemical assays should not be ignored. They are vital for the decision making by clinicians and diagnosis and monitoring of patients, especially those in the intensive care units, grading the severity of the disease, estimating prognosis, and evaluating complications and response to therapy. The following tests are intensively used for patients with COVID-19 during the hospitalization: For diagnosis neutrophil, lymphocyte and eosinophil count, C-reactive protein (CRP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, procalcitonin (PCT) and fibrinogen; for grading severity lymphocyte count, LDH, creatine kinase MB isoenzyme, cardiac troponins, brain natriuretic peptide (BNP) or NT-proBNP, D-dimer, fibrinogen, CRP, PCT, LDH, prothrombin time (PT) and activated prothrombin time (APTT); for prognosis increased D-dimer, decreased thrombocyte count, cerebrospinal fluid (CSF) interleukin-6 (IL-6), CSF IL-8, CSF tumor necrosis factor α (TNFα) and CSF β2-microglobulin; for monitoring of treatment response decreased LDH, CK, CRP, AST and ALT; and for complications increased PCT, CRP, ferritin, D-dimer, IL-2, IL-7, TNFα, fibrinogen, APTT and PT.

These parameters were overused in practice and some stock and supply problems happened in clinical laboratories.

Another important issue during the pandemic is to take protective measures to prevent staff from getting sick with a very contagious virus. For this aim guidelines were prepared and shared with laboratory specialists and environment.

Education and training of medical biochemistry residents without any interruption was also an indispensable task for all education and training units. Therefore, many webinars, courses, and conferences were organized by the use of distance learning techniques in the digital environment. We had to learn distance learning techniques and the pandemic pushed us to learn these newly developing learning techniques.

In this book, all these aspects of the contribution of medical biochemistry to a serious general public health problem and emerging opportunities in education and training are discussed by my competent colleagues.

In conclusion, there is no doubt that the COVID-19 pandemic has highlighted the critical role of laboratory medicine in general and medical biochemistry in particular (I hope the central authority, the Ministry of Health, can also see this reality and restores the personal rights of laboratory specialists and workers in Turkey).

Whatever the conditions, medical laboratory staff will continue to play a vital role in the screening, diagnosis, monitoring, and treatment of SARS-CoV-2 infection.

We believe that laboratory scientists along with all medical professionals, industry, and the public health authority, altogether will overcome the pandemic eventually.

I would like to thank all my colleagues for contributing to this book.

I would like to thank Türkiye Klinikleri for giving this opportunity to the Turkish Biochemical Society.

And, last but not least, I would like to dedicate this book to healthcare workers who died from the pandemic.

With my best wishes and regards.

Prof. Dr. Doğan YÜCEL
Editor

REFERENCES

1. Yilmaz E, Akyön Y, Serdar M. The molecular footprints of COVID-19. Turk J Biochem. 2020;45(3):241-8.
2. Saatçi E. Newly developed diagnostic methods for SARS-CoV-2 detection. Turk J Biochem. 2020;45(5):465-74.
3. Adeli K. Critical role of laboratory medicine in the global response to the COVID-19 pandemic. Clin Chem Lab Med. 2020;58(7):1019- 20.
4. Lippi G, Horvath A, Adeli K. Editorial and executive Summary: IFCC Interim Guidelines on clinical laboratory testing during the COVID19 pandemic. Clin Chem Lab Med. 2020;58(12):1965-9.
5. Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated withCOVID-19 disease progression. Crit Rev Clin Lab Sci. 2020;57(6):389-99.
6. Tomo S, Karli S, Dharmalingam K, Yadav D, Sharma P. The clinical laboratory: a key player in diagnosis and management of COVID19. eJIFCC. 2020;31(4):326-46.
7. Yucel M, Avsar C. The effect of COVID-19 pandemic on biochemistry test consumption numbers and variety. Turk J Biochem. 2020;45(3):339-41.
8. Zengi O, Aykal G, Coskun C, Serdar M, Yucel D. COVID-19 laboratory biosafety guide. Turk J Biochem. 2020;45(3):461-3.

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