COVID-19 Hastalarının Tanı, Tedavi ve Takibinde Klinik Biyokimya Laboratuvarlarının Rolü
Yıl 2022,
Cilt: 31 Sayı: 1, 1 - 9, 31.03.2022
Tuğba Polat
,
Gülçin Dağlıoğlu
,
Ozl Gorur
,
Tamer Cevat İnal
Öz
Dünya sağlık örgütü tarafından COVID-19’un pandemi olarak ilan edildiği 11 Mart 2020’den bu yana vaka sayıları tüm dünyada giderek artmış olup bu kontrolsüz artış sağlık sistemleri üzerinde büyük bir yük oluşturmuştur. Tüm dünyada hastalığın yayılımını önlemek amacıyla milyarlarca insan için karantina gibi sert önlemler alınmıştır. Bu da özellikle ülkelerin ekonomi ve sağlık sistemlerini olumsuz etkilemiştir ve etkilemeye de devam etmektedir. Özellikle, asemptomatik COVID-19 vaka oranlarının yüksek olması nedeniyle alınan önlemler yetersiz kalmakta ve pandemi ile mücadeleyi zorlaştırmaktadır. Nükleik asit amplifikasyon testi, SARS-CoV-2 enfeksiyonunun tanısında altın standart yöntemdir. Ancak sonuç verme süresinin uzun olması, %40’a varan yanlış negatiflik oranı nedeniyle hastaların hızlı şekilde taranması, tedaviye başlanması gecikmektedir. Erken dönemde hastaların biyokimyasal testler ile değerlendirilerek tanı ve tedavilerinin hızlandırılması hem hastalığın erken dönem kontrolü açısından hem de salgının yayılımının kontrolü ile salgın sırasında kaynakların doğru ve verimli kullanılması açısından önem taşımaktadır.
Bu derleme ile; hastalığın tanısında, takibinde, hasta için uygun tedavinin düzenlenmesinde kullanılan biyokimyasal testler ile hastalığın prognozunun belirlenmesine yönelik oluşturulan risk tahmin skorlarında kullanılan biyokimyasal testlerin özetlenmesi amaçlanmıştır.
Kaynakça
- 1. Ferrari D, Motta A, Strollo M, Banfi G, Locatelli M. Routine blood tests as a potential diagnostic tool for COVID-19. Clin Chem Lab Med. 2020;58:1095-99.
- 2. World Health Organisation. Coronavirus disease (COVID-19) pandemic. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed: February 2021.
- 3. Çöl M, Güneş G. COVID-19 salgınına genel bir bakış. In: COVID-19 (Eds Memikoğlu O, Genç V): 1-9. Ankara, Ankara Üniversitesi Basımevi, E-Kitap, 2020.
- 4. Wang F, Hou H, Wang T, Luo Y, Tang G, Wu S, et al. Establishing a model for predicting the outcome of COVID-19 based on combination of laboratory tests. Travel Med Infect Dis. 2020;36:101782.
- 5. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical featrures of patients infected with 2019 novel coronavirus in Wuhan China. Lancet. 2020;395:497-506.
- 6. Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58:1021-28.
- 7. Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci. 2020;57:389-99.
- 8. SARS-CoV-2 pandemi sürecinde nasıl değişiyor ve bu bize ne anlatıyor? https://sarkac.org/2020/03/sars-cov-2-pandemi-surecinde-nasil-degisiyor/. Accessed: February 2021.
- 9. Bourgonje AR, Abdulle AE, Timens W, Hillebrands JL, Navis GJ, Gordijn SJ, et al. Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol. 2020;251:228-48.
- 10. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol.2004;203: 631-37.
11. Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med. 2020;288:192-206.
- 12. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507-13.
- 13. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes ofcritically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8:475-81.
- 14. Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26:681-87.
- 15. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-62.
- 16. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state. JAMA. 2020;323:1612-1614.
- 17. O'Shea PM, Lee GR, Griffin TP, Tormey V, Hayat A, Costelloe SJ, et al. COVID-19 in adults: test menu for hospital blood science laboratories. Ir J Med Sci. 2020;189:1147-52.
- 18. Eljilany I, Elzouki AN. D-Dimer, Fibrinogen, and IL-6 in COVID-19 Patients with Suspected Venous Thromboembolism: A Narrative Review. Vasc Health Risk Manag. 2020;16:455-62.
- 19. Mucha SR, Dugar S, McCrae K, Joseph D, Bartholomew J, Sacha GL, et al. Coagulopathy in COVID-19: manifestations and management. Cleve Clin J Med. 2020;87:461–68.
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- 22. Schmitt FCF, Manolov V, Morgenstern J, Fleming T, Heitmeier S, Uhle F, et al. Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care. 2019;9(1):19.
- 23. Lippi G, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin Chem Lab Med. 2020;58:1063-69.
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- 26. Pourbagheri-Sigaroodi A, Bashash D, Fateh F, Abolghasemi H. Laboratory findings in COVID-19 diagnosis and prognosis. Clin Chim Acta. 2020;510:475-82.
- 27. Kiss S, Gede N, Hegyi P, Németh D, Földi M, Dembrovszky F, et al. Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis. Med Microbiol Immunol. 2021;210:33-47.
- 28. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J Transl Med. 2020;18:206.
- 29. Salamanna F, Maglio M, Landini MP, Fini M. Platelet functions and activities as potential hematologic parameters related to Coronavirus Disease 2019 (Covid-19). Platelets. 2020;31:627-32.
- 30. Tjendra Y, Al Mana AF, Espejo AP, Akgun Y, Millan NC, Gomez-Fernandez C, et al. Predicting Disease Severity and Outcome in COVID-19 Patients: A Review of Multiple Biomarkers. Arch Pathol Lab Med. 2020;144:1465-74.
- 31. Mina A, van Besien K, Platanias LC. Hematological manifestations of COVID-19. Leuk Lymphoma. 2020;61:2790-98.
- 32. Demelo-Rodríguez P, Cervilla-Muñoz E, Ordieres-Ortega L, Parra-Virto A, Toledano-Macías M, Toledo-Samaniego N, et al. Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb Res. 2020;192:23-26.
- 33. Léonard-Lorant I, Delabranche X, Séverac F, Helms J, Pauzet C, Collange O, et al. Acute pulmonary embolism in COVID-19 patients at CT angiography and relationship to D-dimer levels. Radiology. 2020;296:E189-E191.
- 34. Khan IH, Savarimuthu S, Leung MST, Harky A. The need to manage the risk of thromboembolism in COVID-19 patients. J Vasc Surg. 2020;72:799-804.
- 35. Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020;7:e438-e440.
- 36. Naymagon L, Zubizarreta N, Feld J, van Gerwen M, Alsen M, Thibaud S, et al. Admission D-dimer levels, D-dimer trends, and outcomes in COVID-19. Thromb Res. 2020;196:99-105.
- 37. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844-47.
- 38. Agbuduwe C, Basu S. Haematological manifestations of COVID-19: From cytopenia to coagulopathy. Eur J Haematol. 2020;105:540-46.
- 39. Bowles L, Platton S, Yartey N, Dave M, Lee K, Hart DP, et al. Lupus anticoagulant and abnormal coagulation tests in patients with Covid-19. N Engl J Med. 2020;383:288-90.
- 40. Escher R, Breakey N, Lämmle B. Severe COVID-19 infection associated with endothelial activation. Thromb Res. 2020;190:62.
- 41. Bloom PP, Meyerowitz EA, Reinus Z, Daidone M, Gustafson J, Kim AY, et al. Liver biochemistries in hospitalized patients with COVID-19. Hepatology. 2021;73:890-900.
- 42. Stegeman I, Ochodo EA, Guleid F, Holtman GA, Yang B, Davenport C, et al. Routine laboratory testing to determine if a patient has COVID-19. Cochrane Database Syst Rev. 2020;11: CD013787.
- 43. Xue G, Gan X, Wu Z, Xie D, Xiong Y, Hua L, et al. Novel serological biomarkers for inflammation in predicting disease severity in patients with COVID-19. Int Immunopharmacol. 2020;89(Pt A):107065.
- 44. Shang W, Dong J, Ren Y, Tian M, Li W, Hu J, et al. The value of clinical parameters in predicting the severity of COVID-19. J Med Virol. 2020;92:2188-92.
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- 46. Pan F, Yang L, Li Y, Liang B, Li L, Ye T, et al. Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study. Int J Med Sci. 2020;17:1281-92.
- 47. Gu J, Korteweg C. Pathology and pathogenesis of severe acute respiratory syndrome. Am J Pathol. 2007;170:1136-47.
- 48. Bennouar S, Bachir Cherif A, Kessira A, Hamel H, Boudahdir A, Bouamra A, et al. Usefulness of biological markers in the early prediction of corona virus disease-2019 severity. Scand J Clin Lab Invest. 2020;80:611-18.
- 49. Liang W, Liang H, Ou L, Chen B, Chen A, Li C, et al. Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19. JAMA Intern Med. 2020;180:1081-89.
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- 51. Soy M, Keser G, Atagündüz P, Tabak F, Atagündüz I, Kayhan S. Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol. 2020;39:2085-94.
- 52. Asghar MS, Haider Kazmi SJ, Khan NA, Akram M, Hassan M, Rasheed U, et al. Poor Prognostic Biochemical Markers Predicting Fatalities Caused by COVID-19: A Retrospective Observational Study From a Developing Country. Cureus. 2020;12:e9575.
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The Role of Clinical Biochemistry Laboratories in the Diagnosis, Treatment and Follow-Up of COVID-19 Patients
Yıl 2022,
Cilt: 31 Sayı: 1, 1 - 9, 31.03.2022
Tuğba Polat
,
Gülçin Dağlıoğlu
,
Ozl Gorur
,
Tamer Cevat İnal
Öz
Since 11 March 2020, when COVID-19 was declared as a pandemic by the World Health Organization, the number of cases has increased all over the world and this uncontrolled increase has created a great burden on health systems. Strict measures such as quarantine have been taken for billions of people all over the world to prevent the spread of the disease. This, in particular, has adversely affected the economy and health systems of countries and continues to do so. In particular, due to the high rates of asymptomatic COVID-19 cases, the measures taken remain insufficient and make it difficult to combat the pandemic. Nucleic acid amplification test is the gold standard method in the diagnosis of SARS-CoV-2 infection. However, due to the long duration of giving results and the false negativity rate of up to 40%, the rapid screening of the patients and the initiation of treatment are delayed. Accelerating the diagnosis and treatment of patients by evaluating them with biochemical tests in the early period is important both in terms of early control of the disease and control of the spread of the epidemic and the correct and efficient use of resources during the epidemic.
With this review; it is aimed to summarize the biochemical tests used in the diagnosis, follow-up of the disease, in the regulation of appropriate treatment for the patient, and the biochemical tests used in the risk prediction scores created to determine the prognosis of the disease.
Kaynakça
- 1. Ferrari D, Motta A, Strollo M, Banfi G, Locatelli M. Routine blood tests as a potential diagnostic tool for COVID-19. Clin Chem Lab Med. 2020;58:1095-99.
- 2. World Health Organisation. Coronavirus disease (COVID-19) pandemic. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed: February 2021.
- 3. Çöl M, Güneş G. COVID-19 salgınına genel bir bakış. In: COVID-19 (Eds Memikoğlu O, Genç V): 1-9. Ankara, Ankara Üniversitesi Basımevi, E-Kitap, 2020.
- 4. Wang F, Hou H, Wang T, Luo Y, Tang G, Wu S, et al. Establishing a model for predicting the outcome of COVID-19 based on combination of laboratory tests. Travel Med Infect Dis. 2020;36:101782.
- 5. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical featrures of patients infected with 2019 novel coronavirus in Wuhan China. Lancet. 2020;395:497-506.
- 6. Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58:1021-28.
- 7. Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci. 2020;57:389-99.
- 8. SARS-CoV-2 pandemi sürecinde nasıl değişiyor ve bu bize ne anlatıyor? https://sarkac.org/2020/03/sars-cov-2-pandemi-surecinde-nasil-degisiyor/. Accessed: February 2021.
- 9. Bourgonje AR, Abdulle AE, Timens W, Hillebrands JL, Navis GJ, Gordijn SJ, et al. Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol. 2020;251:228-48.
- 10. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol.2004;203: 631-37.
11. Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med. 2020;288:192-206.
- 12. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507-13.
- 13. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes ofcritically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8:475-81.
- 14. Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26:681-87.
- 15. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054-62.
- 16. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX, Chong M, et al. Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington state. JAMA. 2020;323:1612-1614.
- 17. O'Shea PM, Lee GR, Griffin TP, Tormey V, Hayat A, Costelloe SJ, et al. COVID-19 in adults: test menu for hospital blood science laboratories. Ir J Med Sci. 2020;189:1147-52.
- 18. Eljilany I, Elzouki AN. D-Dimer, Fibrinogen, and IL-6 in COVID-19 Patients with Suspected Venous Thromboembolism: A Narrative Review. Vasc Health Risk Manag. 2020;16:455-62.
- 19. Mucha SR, Dugar S, McCrae K, Joseph D, Bartholomew J, Sacha GL, et al. Coagulopathy in COVID-19: manifestations and management. Cleve Clin J Med. 2020;87:461–68.
- 20. Ak G, Karakabak Bilal P, Bayar MK. Sitokin Fırtınası ve Tromboembolik Olaylar. In: COVID-19 (Eds Memikoğlu O, Genç V): 67-79. Ankara, Ankara Üniversitesi Basımevi, E-Kitap, 2020.
- 21. Levi M, van der Poll T. Coagulation and sepsis. Thromb Res. 2017;149:38-44.
- 22. Schmitt FCF, Manolov V, Morgenstern J, Fleming T, Heitmeier S, Uhle F, et al. Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care. 2019;9(1):19.
- 23. Lippi G, Plebani M. The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks. Clin Chem Lab Med. 2020;58:1063-69.
- 24. International Federation of Clinical Chemistry and Laboratory Medicine. https://www.ifcc.org/resources-downloads/ifcc-information-guide-on-covid-19-introduction/5-biochemical-monitoring-of-covid-19-patients/. Accessed: February 2021.
- 25. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382:1708-20.
- 26. Pourbagheri-Sigaroodi A, Bashash D, Fateh F, Abolghasemi H. Laboratory findings in COVID-19 diagnosis and prognosis. Clin Chim Acta. 2020;510:475-82.
- 27. Kiss S, Gede N, Hegyi P, Németh D, Földi M, Dembrovszky F, et al. Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis. Med Microbiol Immunol. 2021;210:33-47.
- 28. Liu J, Liu Y, Xiang P, Pu L, Xiong H, Li C, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J Transl Med. 2020;18:206.
- 29. Salamanna F, Maglio M, Landini MP, Fini M. Platelet functions and activities as potential hematologic parameters related to Coronavirus Disease 2019 (Covid-19). Platelets. 2020;31:627-32.
- 30. Tjendra Y, Al Mana AF, Espejo AP, Akgun Y, Millan NC, Gomez-Fernandez C, et al. Predicting Disease Severity and Outcome in COVID-19 Patients: A Review of Multiple Biomarkers. Arch Pathol Lab Med. 2020;144:1465-74.
- 31. Mina A, van Besien K, Platanias LC. Hematological manifestations of COVID-19. Leuk Lymphoma. 2020;61:2790-98.
- 32. Demelo-Rodríguez P, Cervilla-Muñoz E, Ordieres-Ortega L, Parra-Virto A, Toledano-Macías M, Toledo-Samaniego N, et al. Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb Res. 2020;192:23-26.
- 33. Léonard-Lorant I, Delabranche X, Séverac F, Helms J, Pauzet C, Collange O, et al. Acute pulmonary embolism in COVID-19 patients at CT angiography and relationship to D-dimer levels. Radiology. 2020;296:E189-E191.
- 34. Khan IH, Savarimuthu S, Leung MST, Harky A. The need to manage the risk of thromboembolism in COVID-19 patients. J Vasc Surg. 2020;72:799-804.
- 35. Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020;7:e438-e440.
- 36. Naymagon L, Zubizarreta N, Feld J, van Gerwen M, Alsen M, Thibaud S, et al. Admission D-dimer levels, D-dimer trends, and outcomes in COVID-19. Thromb Res. 2020;196:99-105.
- 37. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844-47.
- 38. Agbuduwe C, Basu S. Haematological manifestations of COVID-19: From cytopenia to coagulopathy. Eur J Haematol. 2020;105:540-46.
- 39. Bowles L, Platton S, Yartey N, Dave M, Lee K, Hart DP, et al. Lupus anticoagulant and abnormal coagulation tests in patients with Covid-19. N Engl J Med. 2020;383:288-90.
- 40. Escher R, Breakey N, Lämmle B. Severe COVID-19 infection associated with endothelial activation. Thromb Res. 2020;190:62.
- 41. Bloom PP, Meyerowitz EA, Reinus Z, Daidone M, Gustafson J, Kim AY, et al. Liver biochemistries in hospitalized patients with COVID-19. Hepatology. 2021;73:890-900.
- 42. Stegeman I, Ochodo EA, Guleid F, Holtman GA, Yang B, Davenport C, et al. Routine laboratory testing to determine if a patient has COVID-19. Cochrane Database Syst Rev. 2020;11: CD013787.
- 43. Xue G, Gan X, Wu Z, Xie D, Xiong Y, Hua L, et al. Novel serological biomarkers for inflammation in predicting disease severity in patients with COVID-19. Int Immunopharmacol. 2020;89(Pt A):107065.
- 44. Shang W, Dong J, Ren Y, Tian M, Li W, Hu J, et al. The value of clinical parameters in predicting the severity of COVID-19. J Med Virol. 2020;92:2188-92.
- 45. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;71:762-68.
- 46. Pan F, Yang L, Li Y, Liang B, Li L, Ye T, et al. Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study. Int J Med Sci. 2020;17:1281-92.
- 47. Gu J, Korteweg C. Pathology and pathogenesis of severe acute respiratory syndrome. Am J Pathol. 2007;170:1136-47.
- 48. Bennouar S, Bachir Cherif A, Kessira A, Hamel H, Boudahdir A, Bouamra A, et al. Usefulness of biological markers in the early prediction of corona virus disease-2019 severity. Scand J Clin Lab Invest. 2020;80:611-18.
- 49. Liang W, Liang H, Ou L, Chen B, Chen A, Li C, et al. Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19. JAMA Intern Med. 2020;180:1081-89.
- 50. Liao D, Zhou F, Luo L, Xu M, Wang H, Xia J, et al. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: a retrospective cohort study. Lancet Haematol. 2020;7:e671-e678.
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