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Diagnostics

April 13, 2020: COVID-19 Testing at UConn Health

Contributor: Enrique Ballesteros, MD

What testing is available for COVID-19?
The test for COVID-19 is the Real-Time RT-PCR. The availability of this molecular test has been increasing rapidly across the United States as more manufacturers and laboratories have received Emergency Use Authorization (EUA) from the FDA for its use.

Where is UConn Health sending specimens for COVID19 testing?
Over the past few weeks the UConn clinical laboratory has sent specimens to the CT DPH, Quest Diagnostics, and the Jackson Laboratory (JAX Lab).

Currently, specimens are sent as follows:

  • Inpatients and Hospital Staff: JAX Lab
  • Outpatients and Public: Quest

What are the turnaround times (TAT)?
JAX Lab: 24 hours
Quest: Approximately 4 to 6 days

Is UConn doing any in-house testing for COVID19?
No, we are currently not offering in-house testing for COVID19.
We plan to bring the test in-house on an instrument we already have – the CEPHEID platform (this is the same instrument we test for influenza, RCV, MRSA). We have not received from the vendor the recently FDA approved reagents (test kits) for COVID19 testing. In addition, the reported allocation of reagents to our lab will be very small (due to limited supplies, increased demand, and strict allocation to hospitals), so in the near future this option will only provide some very limited in-house testing.

Are there any other tests/platforms available that UConn is exploring?
Yes, we have reached out to Abbott regarding the recently FDA approved molecular based rapid test called ID NOW. We have not received any notification about availability of this platform. WE continue to work with Abbott to bring this instrument to our laboratory.

What about serology?
Serologic tests are used to identify patients who have developed antibodies (e.g., IgG, IgM) to an infectious pathogen. The UConn Health clinical laboratory will be offering in the near future an IgG test (SARS-CoV-2 IgG assay) for COVID-19. Serologic tests for COVID-19 are currently not recommended for diagnosis in the acute setting (i.e. to determine whether a patient is currently infected) and should not replace RT-PCR. Of note, the immune response to COVID-19 is not yet fully understood, and serologic tests will be negative prior to development of antibodies which may be variable after infection with the virus. Please note positive results with this assay may be due to past or present infection with non-SARS-CoV-2 coronavirus strains.

What are the major roadblocks for laboratory testing for COVID19?
Demand exceeds supplies. While new tests keep coming up and advertised, hospital-based clinical labs continue to face many challenges on availability on various components for testing.

  • Availability of new instruments
  • Availability of reagents/test kits
  • Availability of swabs for collection of specimens

Petherick, A. (2020). Developing antibody tests for SARS-CoV-2. Lancet, 395(10230), 1101-1102. doi:10.1016/S0140-6736(20)30788-1

If you have any comments or questions about COVID-19 testing, please let me know.

Enrique Ballesteros, M.D.
Chair, Department of Pathology and Laboratory Medicine
UConn Health
Office: 860-679-6714; Cell: 860-348-6122

April 13, 2020: SARS-COVID-2 and Acute Kidney Injury (AKI)

Rate of AKI reported in SARS-CoV-2 patients is around 5-8 % 1,2,3,4, some with urinary manifestations (proteinuria, albuminuria, hematuria), with or without evidence of AKI. Outcome data is generally lacking, especially in patients with underlying CKD. Past experiences with CoV (SARS CoV, MERS) kidneys involvement are not very well understood

Pathogenesis of the AKI could be in the setting of either sepsis - cytokine storm syndrome, direct cellular injury due to the virus, or a combination of both

SARS-CoV2 and AKI

  • Hematuria ~ 28%, proteinuria 44 % (even massive albuminuria) reported in patients during hospitalization4
  • Mortality risk, ICU admission and mechanical ventilation all increased when AKI present4
  • Virus most likely binds to ACE-2 receptor, which is highly expressed in the brush border of proximal tubular cells, less in podocytes, and not in glomerular endothelial and mesangial cells
  • Post mortem tissue analysis showed evidence of virus in tubular epithelium and podocytes. Parenchymal infection of tubular epithelial cells and podocytes, with marked acute tubular injury and sometimes necrosis. No evidence of vasculitis, interstitial inflammation or hemorrhage5

SARS-CoV, and MERS-CoV and AKI

  • Acute kidney injury (AKI) developed in ~ 7 % of SARS-CoV cases and carried a high ~ 92% mortality rate vs ~ 9 % if no renal impairement6
  • Post mortem renal tissue analysis did not detect SARS-COV ultrastructurally, yet PCR fragments of CoV found in urine in 21-50 % of patients. Pathology findings consistent with ATN in all samples with no evidence of glomerular involvement or interstitial infiltrate6
  • Angiotensin converting enzyme-2 and dipeptidyl peptidase-4, both expressed on renal tubular cells, were identified as likely binding partners for SARS-CoV and MERS-CoV7
  • MERS-CoV associated AKI, limited statistical data available, not very common in general, no post mortem renal tissue data found7

Recommendations

Early screening for possible viral kidney involvement in otherwise relatively stable patient. In addition to routine blood tests, obtain complete automated urinalysis testing with microscopic urine sediment examination, urine protein creatinine ratio, urine microalbumin creatinine ratio, sodium, creatinine, and urea nitrogen in random urine samples. Establish early intervention strategy to avoid complications.