CME INDIA Presentation by Dr N K Singh, Admin, CME INDIA.

See two very interesting COVID Scenarios.

Scenario 1:

Case by Dr Bijay Patni, Diabetologist, Kolkata.

All 8 members of a family got Positive. This is report of a 24-year female. Date 25/07/20.

Gets fever, cough. rt PCR positive.

Took only HCQ/Recovers well. Later—-07/08/2020 IGG Antibody – POSITIVE.

COVID-19 Diagnostic Dilemma
COVID-19 Diagnostic Dilemma

Dated 29/08/20 COVID Antibody Positive and Dated 09/08/20 Rt PCR -Negative

Please look carefully at confusing case report… Patient wanted to have small surgical procedure, went to the hospital at Kolkata. At the same time, Anti-SARS-COV2 Reactive dated 17/9/20. Same day rt PCR ……POSITIVE/ NO symptoms👇

COVID-19 Diagnostic Dilemma

How to interpret this case/ Tertial hospital is refusing to do the surgery…

CME INDIA Discussion:

Dr Basab Ghosh, Agartala: RT-PCR can show positivity up to 45 days due to presence of viral particles, even some reports say up to 90 days! If post COVID with presence of antibodies, then specific screening for reinfection could be the protocol now.

Dr N K Singh: But she become negative in between.

Dr Basab Ghosh, Agartala: That sample was not holding viral particles.

Dr N K Singh: Then, why this tertiary hospital, not doing the surgery, they also know the story of dead particle. Why is it not REINFECTION?

Dr Basab Ghosh, Agartala: Retesting is a confusion; Dr Shashank Joshi told several times here itself. Because of defective protocol as on date. We need to see differently, not by regular RT-PCR

Dr Harishkesh: Dead viral element amplification. No wonder UK has asked CT values above 30 to be documented negative for SARS CoV2.

Dr Prabhat Agarwal, Agra: Does it changes with country to country?

Dr Harishkesh: CT Values actually are different for different countries and not only kits. 45 cycles of annealing and constitution are allowed. Finding of viral evidence is akin to finding needle in a haystack. You may get lucky finding the viral genome marker light up in the 15th cycle or maybe the 45th (the max allowed number of cycles generally). Many western countries found that they were over reporting cases and overwhelming the health care … Erroneously counting a CT of 30 and above positive.

Dr Shashank Joshi, DM, Endo, Mumbai: Virus can shed up to 3 months we have many such cases but antibodies IgG document the exposure so I think we need to educate everyone better. As far as surgery is concerned, if emergency go ahead. If elective depends on the hospital and the case.

Dr Pankaj Singhal, MD, Kota: Please comment on CT value of 32. Patient appears to have mild infection or is in recovery phase.

Dr Saagar: Can we ask the microbiology lab for the CT value of both the samples? (Higher values can indicate that it might be false positive). Another variant can be sampling error.

Dr Kapil Sud.Internist Aligarh: Isn’t that presence of antibodies is sufficient to declare the patient non-infective.

Dr V P Youmash, Assistant professor, KAPV medical college, Trichy: Antibody testing reliability also varies from lab to lab, also some studies effective antibodies are not formed in all recovered COVID positive patients too.

Dr Kapil Sud, Internist, Aligarh: In the present case antibodies are positive.

Dr V P Youmash, Assistant professor, KAPV medical college, Trichy: Then the issue they worried is reinfection…the hospital doesn’t want to take risk.

Dr Bhanu Pratap Singh, Physician, Siwan, Bihar: This case is really interesting, but possible explanations are –

  1. Patient developed antibodies to COVID in due course clearly points that patient was infected. But second RTPCR was negative, may be due to sampling error, because even with expertise, in nasopharyngeal material, test positivity is only up to 63%.
  2. As viral particles are shed for a pretty long time (up to 3months as per some reports), this may be the cause for RTPCR positivity for the second time on 29.8.20.
  3. Next question is regarding reinfection. Well in this case antibody titres are low, but what should be its concentration to prevent reinfection is not defined. But we know that FDA has defined an antibody concentration of minimum 6.5 AU/ml in convalescent plasma of donors for treatment of COVID cases with convalescent plasma therapy. However, whether this concentration level is also to prevent re infection is not clear.
  4. In this case antibody titre is low but patient is asymptomatic so, this patient should not be considered reinfected, rather she is non-infective and definitely should be considered for surgery.

Scenario 2:

Case by Dr Somnath, Director & Chief Medicine and Critical Care, Hyderabad

Two of my patients aged 79 yr./ M and 75 yr./ F –  husband and wife – with comorbidities still positive both rapid antigen and RT PCR. Symptomatically much better. Can go for cataract surgery (husband) and diabetic foot minor surgery (wife). Please opine with evidence.

CME INDIA Discussion:

Dr Shashank Joshi DM Endo, Mumbai: 10 days.

Dr N K Singh: So, 14 days concept is not required.

Dr Basab Ghosh, Agartala: Still neighbour, office ask for 14 days, but as Dr Shashank sir said 10 days is scientifically correct. Even physically, you feel free after 10th or 11th day.

Dr Meena Chabra, Diabetologist, Delhi: Cataract is not an emergency surgery, should wait. Foot surgery in local or without anaesthesia can be done. If emergency, then? Neurosurgical emergency surgeries being done in COVID positive.

Dr Arvind Kr Arya, Jamshedpur: Aged patient with comorbid & RTPCR +ve should not go for any surgery except in Acute Emergency like Gun Shot, etc.

Dr Somnath, Hyderabad: We all are discussing about emergency surgeries only. I want to know if done routinely, are there chances of infecting/ spread of COVID and chances of deterioration of patient symptoms related to COVID. Any studies on these. Positive on 9th day of treatment.

Dr Shashank Joshi DM Endo, Mumbai: As per CDC the virus is non-replicative in 10 days, an asymptomatic positive would have no issue after 10 days. In symptomatic cases, usually 14 to 17 days or case to case basis decisions can be taken.

Dr R K Misra, Diabetologist, Jamshedpur:  One Med Rep admitted in COVID Ward more than 2 months continue to be Rapid Antigen E positive and he is not being discharged from Hospital what to do?

Dr Prabhat Agarwal, Consultant physician, Agra: Should go for rdrp/ s / n / orf Gene by rt PCR.

Dr Shashank Joshi DM Endo, Mumbai: He is possibly shedding dead virus particles; you need to do an antibody IgG test to document and stool PCR also may help. E is only a screen tool.

Dr R K Misra, Jamshedpur: Patient was admitted earlier in ICU but now in COVID Ward and doctors there not discharging him as he is Rap E is positive they are saying unless his Rapid E antigen becomes negative they will not discharge, no oxygen requirement and he cannot take DAMA, legal issue.

Dr Satish Kumar, Cardiologist, Bokaro: Sir, what’s RapE, Is it Rapid Antigen? If it was positive, then it’s COVID positive. If it’s is E-gene, them it’s not confirmed COVID. Also, the discharge policy has been changed recently in Jharkhand. A negative report after 10 days for asymptomatic patients not mandatory.

Dr S K Saxsena: How much Rapid Antigen Test is reliable?

CME INDIA Learning Points:

  • Based on evidence showing the rarity of virus that can be cultured in respiratory samples after 9 days of symptom onset, especially in patients with mild disease, usually accompanied by rising levels of neutralizing antibodies and a resolution of symptoms, it appears safe to release patients from isolation based on clinical criteria that require a minimum time in isolation of 13 days, rather than strictly on repeated PCR results.
  • It is important to note that the clinical criteria require that patients’ symptoms have been resolved for at least three days before release from isolation, with a minimum time in isolation of 13 days since symptom onset.
  • Although the risk of transmission after symptom resolution is likely to be minimal based on what is currently known, it cannot be completely ruled out. However, there is no zero-risk approach, and strict reliance on PCR confirmation of viral RNA clearance creates other risks. (WHO-Updated).

CME INDIA Tail Piece:

Understanding Rapid Antigen test and Antibody Test(Updated)

Sethuraman, N., Jeremiah, S. S. & Ryo, A. J. Am. Med. Assoc. 323, 2249–2251 (2020)

RAPID ANTIGEN TEST (CDC – Updated on 4th September 2020)

  • The FDA has granted emergency use authorization (EUA) for antigen tests that can identify SARS-CoV-2.
  • Antigen tests are immunoassays that detect the presence of a specific viral antigen, which implies current viral infection. Antigen tests are currently authorized to be performed on nasopharyngeal or nasal swab specimens placed directly into the assay’s extraction buffer or reagent.
  • Antigen tests are relatively inexpensive and can be used at the point-of-care. The currently authorized devices return results in approximately 15 minutes. Antigen tests for SARS-CoV-2 are generally less sensitive than viral tests that detect nucleic acid using reverse transcription polymerase chain reaction (RT-PCR).
  • Rapid antigen tests perform best when the person is tested in the early stages of infection with SARS-CoV-2 when viral load is generally highest. They also may be informative in diagnostic testing situations in which the person has a known exposure to a confirmed case of COVID-19. Rapid antigen tests can be used for screening testing in high-risk congregate settings in which repeat testing could quickly identify persons with a SARS-CoV-2 infection to inform infection prevention and control measures, thus preventing transmission.
  • The “gold standard” for clinical diagnostic detection of SARS-CoV-2 remains RT-PCR. Thus, it may be necessary to confirm a rapid antigen test result with a nucleic acid test, especially if the result of the antigen test is inconsistent with the clinical context. When confirming an antigen test result with a RT-PCR test, it is important that the time interval between collection of samples for the two tests is less than two days, and there have not been any opportunities for new exposures between them.
  • The sensitivity of rapid antigen tests is generally lower than RT-PCR. The first antigen tests to have received FDA EUAs demonstrate sensitivity ranging from 84.0%-97.6% compared to RT-PCR. Antigen levels in specimens collected beyond 5-7 days of the onset of symptoms may drop below the limit of detection of the test. This may result in a negative test result, while a more sensitive test, such as RT-PCR, may return a positive result.
  • The specificity of rapid antigen tests is generally as high as RT-PCR – the first antigen tests that have received FDA EUAs have reported specificity of 100% – which means that false positive results are unlikely. 
  • The sensitivity of current FDA-authorized antigen tests varies, and thus negative diagnostic testing results should be handled differently depending on the testing device and its stated performance characteristics. In most cases, negative antigen diagnostic test results are considered presumptive. CDC recommends confirming negative antigen test results with an RT-PCR test when the pre-test probability is relatively high, especially if the patient is symptomatic or has a known exposure to a person confirmed to have COVID-19. Ideally, confirmatory RT-PCR testing should take place within two days of the initial antigen testing.

New Guidelines on ANTIBODY Test (Updated 15/09/2020)

The Infectious Diseases Society of America (IDSA) recommendations:

  1. The panel suggests against using serologic testing to diagnose COVID 19 infection during the first 2 weeks (14 days) following symptom onset (conditional recommendation, very low certainty of evidence)
  2. When COVID 19 infection requires lab confirmation panel suggests testing for COVID 19 IgG or total antibody 3 to 4 weeks after symptom onset to detect evidence of past infection (conditional recommendation, very low certainty of evidence). When serology is being considered as an adjunct to nucleic acid amplification tests for diagnosis, testing 3 to 4 weeks post-symptom onset maximises the sensitivity and specificity to detect past infection. Serosurveillance studies should use assays with high specificity, especially when the prevalence of SARS-CoV-2 in the community is expected to be low (≤1%).
  3. The panel makes no recommendation either for or against using IgM antibodies to detect evidence of past COVID 19 infection (conditional recommendation, very low certainty of evidence
  4. The panel suggests against using IgA antibodies to detect evidence of past COVID 19 infection (conditional recommendation, very low certainty of evidence)
  5. The panel suggests against using IgM or IgG antibody combination tests to detect evidence of past COVID 19 infection (conditional recommendation, very low certainty of evidence). IgM or IgG combination tests are those where detecting either antibody class is used to define a positive result.
  6. The panel suggests using IgG antibody to provide evidence of COVID-19 infection in symptomatic patients with a high clinical suspicion and repeatedly negative NAAT testing (weak recommendation, very low certainty of evidence). When serology is being considered as an adjunct to NAAT for diagnosis, testing 3 to 4 weeks post-symptom onset maximises the sensitivity and specificity to detect past infection.
  7. In paediatric patients with multisystem inflammatory syndrome, the IDSA panel suggests using both IgG antibody and NAAT to provide evidence of current or past COVID-19 infection (strong recommendation, very low certainty of evidence).
  8. The IDSA panel makes no recommendation for or against using capillary versus venous blood for serologic testing to detect SARS-CoV-2 antibodies (knowledge gap).

Serologic tests should not be used to determine immunity or risk of re-infection. AntiSARS-CoV-2 antibody detection cannot inform decisions to discontinue physical distancing or lessen the use of personal protective equipment.

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