This is a retrospective, non interventional cohort study using stored plasma samples fromappoximately 300 adults hospitalized with confirmed COVID 19. Baseline suPAR measuredusing the suPARnostic TurbiLatex assay on the Roche cobas c501.
The Michigan Medicine COVID-19 Cohort (M2C2) is the largest sub-cohort of the
International Study on Inflammation in COVID-19 (ISIC). The M2C2 comprises consecutive,
systematically enrolled adults (≥18 years) with confirmed SARS-CoV-2 infection
hospitalized specifically for COVID-19 at the University of Michigan from 1 February 2020
to 1 June 2021. Adult patients hospitalized in participating U.S. hospitals with
confirmed COVID 19 infection during the study period, who had baseline suPAR measured
using the suPARnostic TurbiLatex assay on Roche cobas c501 on plasma samples obtained
within 48 hours of admission. The cohort reflects real world U.S. data and includes
racially and ethnically diverse populations with typical U.S. burdens of obesity,
diabetes, and chronic kidney disease.
SAMPLE SIZE JUSTIFICATION - Since we have a fixed 6 ng/mL threshold and are only
validating (not discovering), the analysis is just a 2×2 table.
True sensitivity 94% (matching SPARCOL): N=136 is enough True sensitivity 90%
(conservative): N=237 is enough True sensitivity 88% (worst case): N=440 needed SPARCOL
showed 93.9%, so N=300 covers you even if U.S. sensitivity drops to ~88% - a generous
safety margin.
STATED LIMITATIONS
- N=300 does not support fully adjusted multivariable logistic regression
- Hispanic and Asian subgroups are too small for standalone powered analyses. These
subgroups are reported descriptively.
- Formal non-inferiority testing of sensitivity (U.S. vs. SPARCOL) would require a
larger sample. The comparison is performed descriptively, with the acceptance
criterion applied to the U.S. data independently (lower 95% CI > 80%).
CONCLUSION We have previously considered measuring 1200 samples, but a balance between
statistical rigor and practical feasibility (assay cost, data extraction effort) we
recalculated number needed to N=300 which according to the power calculation is an
appropriate sample size for this validation study.
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Diagnostic Test: suPARnostic® TurbiLatex Assay on Roche cobas c501
Quantitative measurement of soluble urokinase plasminogen activator receptor (suPAR) in
human EDTA plasma using the suPARnostic TurbiLatex particle enhanced turbidimetric
immunoassay performed on the Roche Diagnostics cobas c501 analyzer. Results are reported
in ng/mL and interpreted using a pre specified clinical threshold of 6 ng/mL to identify
patients at increased risk for progression to severe respiratory failure.
- Inclusion Criteria
1. Age ≥18 years at hospital admission.
2. Confirmed SARS CoV 2 infection documented in the EHR (positive RT PCR or
antigen test from a respiratory specimen).
3. suPAR level measured from EDTA plasma using the suPARnostic TurbiLatex assay on
a Roche cobas c501 analyzer on samples taken within 24 hours of Emergency
Department presentation or hospital admission.
4. Available 30 day follow up data from the date of admission (30 day vital status
and SRF status ascertainable).
- Exclusion Criteria
1. Already intubated and/or receiving invasive mechanical ventilation at the time
of suPAR sample collection.
2. Documented "Do Not Intubate" order or determination that the patient was not a
candidate for mechanical ventilation at admission.
3. suPAR measured by a method other than the suPARnostic TurbiLatex assay on Roche
cobas c501 (e.g., ELISA, other platforms).
4. Incomplete primary endpoint data (SRF status cannot be determined within 30
days).
5. Patients with confirmed SARS CoV 2 infection who were not primarily admitted
for COVID 19 (incidental positive test in a non COVID admission).
Michigan state university, Department of Biostatistics
Ann Arbor, Michigan, United States
Not Provided