The diagnosis of COVID‐19 requires integration of clinical and laboratory data. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) diagnostic assays play a central role in diagnosis and have fixed technical performance metrics. Interpretation becomes challenging because the clinical sensitivity changes as the virus clears and the immune response emerges. Our goal was to examine the clinical sensitivity of two most common SARS‐CoV‐2 diagnostic test modalities, polymerase chain reaction (PCR) and serology, over the disease course to provide insight into their clinical interpretation in patients presenting to the hospital. We conducted a single‐center, retrospective study. To derive clinical sensitivity of PCR, we identified 209 PCR‐positive SARS‐CoV‐2 patients with multiple PCR test results (624 total PCR tests) and calculated daily sensitivity from date of symptom onset or first positive test. Clinical sensitivity of PCR decreased with days post symptom onset with >90% clinical sensitivity during the first 5 days after symptom onset, 70%‐71% from Days 9 to 11, and 30% at Day 21. To calculate daily clinical sensitivity by serology, we utilized 157 PCR‐positive patients with a total of 197 specimens tested by enzyme‐linked immunosorbent assay for IgM, IgG, and IgA anti‐SARS‐CoV‐2 antibodies. In contrast to PCR, serological sensitivity increased with days post symptom onset with >50% of patients seropositive by at least one antibody isotype after Day 7, >80% after Day 12, and 100% by Day 21. Taken together, PCR and serology are complimentary modalities that require time‐dependent interpretation. Superimposition of sensitivities over time indicate that serology can function as a reliable diagnostic aid indicating recent or prior infection.

A common functional variant in paraoxonase 1 (PON1), Q192R, was recently reported to be a major determinant of clopidogrel response. This variant was genotyped in 566 participants of the Amish Pharmacogenomics of Anti-Platelet Intervention (PAPI) study and in 227 percutaneous coronary intervention (PCI) patients. Serum paraoxonase activity was measured in a subset of 79 PAPI participants. PON1 Q192R was not associated with pre- or post-clopidogrel platelet aggregation in the PAPI study (P = 0.16 and P = 0.21, respectively) or the PCI cohort (P = 0.47 and P = 0.91, respectively). The Q192 allele was not associated with cardiovascular events (hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.20–1.06; P = 0.07). No correlation was observed between paraoxonase activity and post-clopidogrel platelet aggregation (r2 < 0.01, P = 0.78). None of 49 additional PON1 variants evaluated was associated with post-clopidogrel platelet aggregation. These findings do not support a role for PON1 as a determinant of clopidogrel response.

Introduction: The diagnosis of COVID-19 requires integration of clinical and laboratory data. SARS-CoV-2 diagnostic assays play a central role in diagnosis and have fixed technical performance metrics. Interpretation becomes challenging because the clinical sensitivity changes as the virus clears and the immune response emerges. Our goal was to examine the clinical sensitivity of two most common SARS-CoV-2 diagnostic test modalities, polymerase chain reaction (PCR) and serology, over the disease course to provide insight into their clinical interpretation in patients presenting to the hospital. Methods: A single-center, retrospective study. To derive clinical sensitivity of PCR, we identified 209 PCR-positive SARS-CoV-2 patients with multiple PCR test results (624 total PCR tests) and calculated daily sensitivity from date of symptom onset or first positive test. To calculate daily clinical sensitivity by serology, we utilized 157 PCR-positive patients with a total of 197 specimens tested by enzyme-linked immunosorbent assay for IgM, IgG, and IgA anti-SARS-CoV-2 antibodies. Results: Clinical sensitivity of PCR decreased with days post symptom onset with >90% clinical sensitivity during the first 5 days after symptom onset, 70-71% from days 9-11, and 30% at day 21. In contrast, serological sensitivity increased with days post symptom onset with >50% of patients seropositive by at least one antibody isotype after day 7, >80% after day 12, and 100% by day 21. Conclusion: PCR and serology are complimentary modalities that require time-dependent interpretation. Superimposition of sensitivities over time indicate that serology can function as a reliable diagnostic aid indicating recent or prior infection.