FOLLOW-UP OF COVID-19

ANOTHER COVID-19 reference?

 

This document intends to give a comprehensive overview of clinical laboratory tests that can be used in the follow-up of the disease and to assess the outcome for the patients.

 

With a number of vaccination strategies now being rolled out over the world, the pandemic SARS-CoV-2 may appear to be under control. However, the prospect of persistent and
seasonal COVID-19 is real1. This means that the follow-up of patients will still be needed for the considerable future.

Tosoh’s immunoassay analysers offer a substantial number of test that allow a fast, sensitive and easy way to assess and monitor COVID-19 patients.

 

PITUITARY, ADRENAL, THYROID AND GONADAL BIOMARKERS

 

The following biomarkers playing a role during SARS-CoV-2 infection ( Ponti et al.3)shutterstock_1281336226-1-2

Haematological (lymphocyte count, neutrophil count, neutrophil–lymphocyte ratio (NLR))

  • Inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)) Presepsin (Fukudat et 45)
  • Immunological (Interleukin 6 (IL-6))
  • Biochemical (D-dimer, Troponin, creatine kinase (CK), aspartate aminotransferase (AST))
  • Especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS).

 

 

 

VITAMIN D

 

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T-regulatory lymphocyte levels have been reported to be low in many COVID-19 patients and can be increased by vitamin D supplementation. (Weir et al7)

ACCURATE MEASUREMENT OF VITAMIN D CAN PREDICT THE SUSCEPTIBILITY TO AND THE PROGRESS OF THE COVID-19 DISEASE

 

 

 

 

 

 

FERRITIN

 

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Khourssaji et al16 concluded that Ferritin is increased in 92% of male and female COVID-19 patients.

 

Serum Ferritin may be considered both a prognostic and stratifying biomarker that can also contribute to therapeutic decision-making concerning patients with COVID-19 according to Kappert et al15.

 

 

EVIDENCE IS INCREASING IN THE LITERATURE FOR FERRITIN AS BEING AN EARLY MARKER OF SEVERITY IN COVID-19 PATIENTS 

 

CYSTATIN C

 

Cystatin C was significantly increased in 82 survivors and 25 non-survivors with

COVID-19 (Ouyang19).

Serum Cystatin C was significantly higher in imaging progression patients compared to those in imaging progression-free ones (Yang et al18).

 

AMONG OTHER MARKERS, CYSTATIN C CAN BE MEASURED TO ASSESS THE SEVERITY OF COVID-19 DISEASE

 

CORTISOL

 

cortisol-structure

Bellastella et al5 and Somasundaram et al6 demonstrated the impact of SARS-CoV-2 infection on the pituitary–adrenal axis function.

 

ALTHOUGH RESULTS SHOULD BE INTERPRETED WITH CARE, CORTISOL CAN BE A PREDICTOR OF COVID-19 MORTALITY


 

 

 

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CARDIOVASCULAR MARKERS

 

Troponin I (cTnI) values are significantly increased in patients with severe SARS-CoV-2 infection compared to those with milder forms of disease.(Lippi et al22)

 

Guzik et al23 discuss the impact on COVID-19 on cardiovascular complications. 

   

 

 

PRESEPSIN AND SEPSIS

sepsis

 

Similar to sepsis, a dysregulated immune response is responsible for a cascade of events occurring in severe COVID-19 cases. This results in a dynamic process that leads to the activation of the adaptiveimmune system including T lymphocytes and B lymphocytes, which can ultimately lead to cell and tissue necrosis and multiorgan organ dysfunction (Wiersinga et al26, Zafer27).

Fukuda et al43 describe a few cases showing where Presepsin increased immediately following elevation of CRP in the moderate-to-severely ill COVID-19 patients, resulting in invasive mechanical ventilation with exacerbation of COVID-19 pneumonia.

 

 

 

D-DIMER AND COAGULATION

 

Since the onset of the SARS-CoV-2 pandemic an elevated D-dimer <link to D-dimer > at admission (≥1.0 μg/mL) is associated with an increased mortality and D-Dimer continues to rise throughout the course of hospitalization in non-surviving patients (Zhou et al30).

Based on a meta-analysis of 35 publications, Bao et al31 conclude that D-Dimer among other laboratory parameters provide valuable signals for preventing the deterioration of the disease.

 

KL-6

 

dreamstime_xl_70621432 LungKL-6 is a mucinous high-molecular weight glycoprotein, expressed on type 2 pneumonocytes, which is reported to be elevated in the serum and bronchoalveolar lavage fluid of patients with interstital pneumonia. KL-6 could be an indicator to evaluate the progression of COVID-19, which is parallel to the level of lung injury and inflammation in patients according to Xue et al36.

Awano et al38 observed that serum KL-6 levels were significantly elevated in severe COVID-19 and is useful for evaluating its severity.

 

 

 

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References:

1 Murray CJL, Piot P. The Potential Future of the COVID-19 Pandemic: Will SARS-CoV-2 Become a Recurrent Seasonal Infection? JAMA. Published online March 03, 2021. doi:10.1001/jama.2021.2828

3 Ponti G, Maccaferri M, Ruini C, Tomasi A, Ozben T. Biomarkers associated with COVID-19 disease progression. Crit Rev Clin Lab Sci. 2020;57(6):389-399. doi:10.1080/10408363.2020.1770685
5 Bellastella G, Maiorino MI, Esposito K. Endocrine complications of COVID-19: what happens to the thyroid and adrenal glands?. J Endocrinol Invest. 2020;43(8):1169-1170. doi:10.1007/s40618-020-01311-8
6 Somasundaram NP, Ranathunga I, Ratnasamy V, et al. The Impact of SARS-Cov-2 Virus Infection on the Endocrine System. J Endocr Soc. 2020;4(8):bvaa082. Published 2020 Jul 2. doi:10.1210/jendso/bvaa082
7 Weir EK, Thenappan T, Bhargava M, Chen Y. Does vitamin D deficiency increase the severity of COVID-19?. Clin Med (Lond). 2020;20(4):e107-e108. doi:10.7861/clinmed.2020-0301
15 Kappert K, Jahi A, Tauber R, Assessment of serum ferritin as a biomarker in COVID-19: bystander or participant? Insights by comparison with other infectious and non-infectious diseases, Biomarkers, 2020; 25:8, 616-625, DOI: 10.1080/1354750X.2020.1797880
16 Khourssaji M, Chapelle V, Evenepoel A, Belkhir L, Yombi J, van Dievoet M et al, A biological profile for diagnosis and outcome of COVID-19 patients. Clinical Chemistry and Laboratory Medicine (CCLM), vol. 58, no. 12, 2020, pp. 2141-2150. https://doi.org/10.1515/cclm-2020-0626
18 Yang Z, Shi J, He Z, Lü Y, Xu Q, Ye C, Chen S, Tang B, Yin K, Lu Y, Chen X. Predictors for imaging progression on chest CT from coronavirus disease 2019 (COVID-19) patients. Aging (Albany NY). 2020 Apr 10;12(7):6037-6048. doi: 10.18632/aging.102999. Epub 2020 Apr 10. PMID: 32275643; PMCID: PMC7185104.
19 Ouyang SM, Zhu HQ, Xie YN, Zou ZS, Zuo HM, Rao YW, Liu XY, Zhong B, Chen X. Temporal changes in laboratory markers of survivors and non-survivors of adult inpatients with COVID-19. BMC Infect Dis. 2020 Dec 11;20(1):952. doi: 10.1186/s12879-020-05678-0. PMID: 33308159; PMCID: PMC7729703.
22 Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence
from a meta-analysis. Prog Cardiovasc Dis. 2020;63(3):390-391. doi:10.1016/j.pcad.2020.03.001
23 Guzik TJ, Mohiddin SA, Dimarco A, et al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020;116(10):1666-1687. doi:10.1093/cvr/cvaa106
26 Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review [published online ahead of print, 2020 Jul 10]. JAMA. 2020;10.1001/jama.2020.12839. doi:10.1001/jama.2020.12839
27 Zafer, M.M.; El-Mahallawy, H.A.; Ashour, H.M. Severe COVID-19 and Sepsis: Immune Pathogenesis and Laboratory Markers. Microorganisms 2021, 9, 159. https://doi.org/10.3390/microorganisms9010159
30 Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. PMID: 32171076; PMCID: PMC7270627.
31 Bao J, Li C, Zhang K, Kang H, Chen W, Gu B. Comparative analysis of laboratory indexes of severe and non-severe patients infected with COVID-19. Clin Chim Acta. 2020;509:180-194. doi:10.1016/j.cca.2020.06.009
36 Xue M, Zheng P, Bian X, et al. Exploration and correlation analysis of changes in Krebs von den Lungen-6 levels in COVID-19 patients with different types in China [published online ahead of print, 2020 Jun 21]. Biosci Trends. 2020;10.5582/bst.2020.03197. doi:10.5582/bst.2020.03197
38 Awano N, Inomata M, Kuse N, et al. Serum KL-6 level is a useful biomarker for evaluating the severity of coronavirus disease 2019 [published online ahead of print, 2020 Aug 21]. Respir Investig. 2020;S2212-5345(20)30115-5. doi:10.1016/j.resinv.2020.07.004
43 Fukada A, Kitagawa Y, Matsuoka M, Sakai J, Imai K, Tarumoto N, et al. Presepsin as a predictive biomarker of severity in COVID-19: A case series. J Med Virol. 2021 Jan;93(1):99-101. doi: 10.1002/jmv.26164. Epub 2020 Jun 24. PMID: 32530491; PMCID: PMC7307131.
45 Ai Fukada , Yutaro Kitagawa , Masaru Matsuoka , Jun Sakai , Kazuo Imai Norihito Tarumoto , Yuta Orihara , Rieko Kawamura , Shinichi Takeuchi , Shigefumi Maesaki , Takuya Maeda Presepsin as a predictive biomarker of severity in COVID-19: A case series J Med Virol 2021 Jan;93(1):99-101. doi: 10.1002/jmv.26164. Epub 2020 Jun 24.