CME INDIA Presentation by Admin.

Make CRP as your guide in monitoring.

CME INDIA Case Scenario

Dr Monica Gupta, Varanasi (on 03/11/2020):

53-year-old male COVID-19 rtPCR positive, today is day 8, CT- value of 32 has an IL6 of 3492. He has no symptoms Spo2- 97 98, Temp normal CRP-24. Ferritin- normal. LDH- 200. His Ct thorax done twice is normal.

He is on favipiravir. On-Clopidogrel/Aspirin combination Tab Methyl Prednisolone 8mg BD.

What can be the reasons for such high IL 6?

CME INDIA Discussion:

Dr H K Jha, MD, CMO, CGHS, Ranchi: Rule out Secondary bacterial infection: Do Procalcitonin., NLR ratio? Do consider other than lung infection. IL 6 is a proinflammatory marker, not a marker of infection.

Dr Molio, Internist, Maregoan, Goa: Repeat IL6 after 3 days. Rule out and treat secondary infection, Do Procalcitonin, Blood culture.

Clinically patient looks stable. Patient is very stable, not hypoxic, not febrile, not breathless.

CT value suggests less viral load almost nob infective.

Dr P R Parthsarathy, Chest Physician, Chennai: Could lab error be a possibility? Why Medrol was given in this case – asymptomatic, inflammatory markers, SpO2 all are normal, (CT value reported as 32 indicating a low viral load). When all the other inflammatory markers are normal. It has to be rechecked to rule out lab error.

Dr Molio Maregoan, Goa: Agree.

Dr Shashikant Nigam MD Med, Ahmedabad: Delayed assessment of Il6.

Dr Monica Gupta Varanasi: I think it was the way the sample was collected and temperature at which it was maintained.

Dr Rajeev Kumar Gupta, MD Medicine, IMS BHU, Varanasi: Please get rechecked IL6, because there are many cases of lab errors. In a case. I came across IL6 report was 450 though other markers were normal, so I went for retesting. The way very next day in different lab, it was 7.5🙆‍♂and 3rd test 7.2!  Probably this difference is due to some collection or transport error.

Dr Gajanan Repal, DNB Medicine, Dharwad, Karnataka: Nice learning ✅

Dr Sheel Goyal, DNB MED., Goyal Hospital, Jaipur: I have gone similar situation 1 month back. I concluded it as sampling and its handling error.

IL6 is to be measured in serum within 30 min. I think you should recheck with immediate drawn serum sample.

Dr Gajanan Repal, Dharwad: Within 30 minutes…. very difficult.

Dr Basab Ghosh, Agartala: Might be blood sample transported as wrong transportation gives faulty results.

Dr Noni G Singha, Internist, Dibrugarh, Assam: Ideal to repeat the test with proper precautions. Test to be done preferably within one hour or at most 2 hrs. If after clotting sample immediately, serum is not separated, may give false high to the extent of 100 times. Longer the serum remains in contact clotted blood, higher the value of IL6.

Dr Abhisheka Kumar: Rule out sampling error. Wrong tube for sample collection. Repeat from another lab.

Dr Shoaib Ginwala, Internist, Vadodara says: A physician from Valsad who had come in contact with a patient of COVID, but clinically asymptomatic, all inflammatory markers normal, CBC normal, HRCT normal was given an IL6 value of 5500. We collected with precautions and it came 32. In past two days two similar incidents where IL6 of 660 and 1550 when repeated in same day with precautions came 10 and 9 respectively. Just prior to writing this another clinical with IL6 150 was given a result of 10.

We need to run controls to ensure that machines are ok, normally we run three levels of controls to decide that the machine and kit is ok. But here the problem is in collection and processing and transport. So, if your IL6 levels are not correlating clinically please get them rechecked with proper precautions to rule out preanalytical errors, we will be saving some Tocilizumab for actually needy patients. (Courtesy Dr Pranav Desai).

Dr Akash Kr Singh, Vadodara: Please recheck if IL6 values need clinical correlation. Needs good lab with immediate processing facilities.

Dr Atri Gangopadhyay, Pulmonologist, Ranchi:

 IL 6 is a very unpredictable marker, and it is recently being measured, so there is no standardized lab method yet. First, I would advise a repeat sampling. Secondly, we can’t guide our treatment by IL-6 at all, because larger number of studies have proved absolutely no difference with the use of TOCLIZUMAB (anti IL6), So since this notification came, I have stopped performing IL 6 altogether

CME INDIA Learning Points

  1. Collection of sample matters. If you collect in plain red topped tubes and allow to clot and serum is not immediately separated, the clotting process causes rapid release of IL6 and you get falsely very high. The degree of false increase is directly proportional to the amount of time it remains in contact with the clotted cells as varied from 3 to 4 times to 100 times or more. EDTA keeps the level more stable for 24 hours.
  2. Post Tocilizumab IL6 level does not assess the short-term effectiveness of the therapy.
  3. CRP is a better marker to assess the effectiveness of the therapy as its level corelates well.
  4. Why Procalcitonin:
    • Procalcitonin is the pro-peptide of calcitonin devoid of hormonal activity. Under normal circumstances, it is produced in the C-cells of the thyroid gland.
    • In healthy humans, PCT levels are undetectable (< 0.1 ng/mL).
    • During severe infection (bacterial, parasitic, and fungal) with systemic manifestations.
    • PCT levels may rise to over 100 ng/mL, produced mostly by extra-thyroid tissue. PCT is a mediator of inflammation.
    • PCT value remains within reference ranges in patients with non-complicated SARS-CoV-2 infection; any substantial increase reflects bacterial co-infection and the development of a severe form of disease and a more complicated clinical picture.
    • Initial PCT value may be helpful in the determination of illness severity, it may not always be a reliable prognostic indicator.
    • PCT values may be influenced by pre-existing comorbid conditions, such as CKD and congestive heart failure, baseline values may be high.
  5. Be Sensible. You do not need high sounding tests in all cases.
  6. Lymphopenia, neutrophilia, elevated serum alanine aminotransferase and aspartate aminotransferase levels, elevated lactate dehydrogenase, high CRP, and high ferritin levels may be associated with greater illness severity

CME INDIA Tail Piece:

COVID IL 6 - Which Tests on Day 1

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