COVID-19 diagnostics in context

Weissleder, Ralph; Lee, Hakho; Ko, Jina; Pittet, Mikaël J.

doi:10.1126/scitranslmed.abc1931

Cited by 368 publications

(422 citation statements)

References 20 publications

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“…There is considerable interest in moving SARS-CoV-2 diagnostics to evidence-based principles. [6][7][8][9] While clinicians await formal guidance from large, prospective, multi-center studies-which will be challenging during the ongoing pandemic-there is considerable uncertainty surrounding SARS-CoV-2 diagnostics in clinical practice. 3,[10][11][12][13] Using available published data [3][4][5][6][7]12,14 and data presented here from our hospital, we offer the following five diagnostic principles for consideration:…”

Section: Discussionmentioning

confidence: 99%

Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital

et al. 2020

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“…The majority of these studies used in vitro transcribed (IVT) short fragments of the viral genomic RNA ( 10 – 12 ) and showed a detection limit of somewhere between 10 and 100 RNA molecules per reaction. For the detection of SARS-CoV-2 RNA, a few commercial rapid tests have been developed [reviewed in ( 13 )] using isothermal DNA amplification reactions involving proprietary enzyme formulations that are not commercially available in a ready-to-go format. Further, their exact sensitivity is still subject to discussion owing to a lack of studies using sufficiently large numbers of test samples.…”

Section: Introductionmentioning

confidence: 99%

A colorimetric RT-LAMP assay and LAMP-sequencing for detecting SARS-CoV-2 RNA in clinical samples

et al. 2020

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The COVID-19 pandemic caused by the SARS-CoV-2 coronavirus is a major public health challenge. Rapid tests for detecting existing SARS-CoV-2 infections and assessing virus spread are critical. Approaches to detect viral RNA based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) have potential as simple, scalable, and broadly applicable testing methods. Compared to RT-qPCR-based methods, RT-LAMP assays require incubation at a constant temperature, thus eliminating the need for sophisticated instrumentation. Here, we tested a two-color RT-LAMP assay protocol for detecting SARS-CoV-2 viral RNA using a primer set specific for the N gene. We tested our RT-LAMP assay on surplus RNA samples isolated from 768 pharyngeal swab specimens collected from individuals being tested for COVID-19. We determined the sensitivity and specificity of the RT-LAMP assay for detecting SARS-CoV-2 viral RNA. Compared to an RT-qPCR assay using a sensitive primer set, we found that the RT-LAMP assay reliably detected SARS-CoV-2 RNA with an RT-qPCR cycle threshold (CT) number of up to 30, with a sensitivity of 97.5% and a specificity of 99.7%. We also developed a swab-to-RT-LAMP assay that did not require a prior RNA isolation step, which retained excellent specificity (99.5%) but showed lower sensitivity (86% for CT<30) than the RT-LAMP assay. In addition, we developed a multiplexed sequencing protocol (LAMP-sequencing) as a diagnostic validation procedure to detect and record the outcome of RT-LAMP reactions.

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“…RDT #1 and #2 was 100% speci c for both IgM and IgG, but speci city was as low as 88.9% for IgM for RDT#4 and 94.4% for IgG for RDT #3. None of the RDTs we tested are FDA approved, but all of them have a CE Mark for use in the European Union (Weissleder, Lee, Ko, & Pittet, 2020).…”

Section: Discussionmentioning

confidence: 99%

Using prenatal blood samples to validate COVID-19 rapid serologic tests

Alger

Cafferata

Alvarado³

et al. 2020

Preprint

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IntroductionBackground cross-reactivity with other coronaviruses may reduce the specificity of COVID-19 rapid serologic tests. Blood collected during prenatal care is a unique source of population-based samples appropriate for validation studies. We used stored 2018 serum samples from an existing pregnancy cohort study to evaluate the specificity of COVID-19 serologic rapid diagnostic tests. MethodsWe randomly selected 120 stored serum samples from pregnant women enrolled in a cohort in 2018, at least one year before the COVID-19 pandemic. We used stored serum to evaluate four lateral flow rapid diagnostic tests, following manufacturers’ instructions. Pictures were taken for all tests and read by two blinded trained evaluators. Results We evaluated 120, 80, 90, and 90 samples, respectively. Specificity for both IgM and IgG was 100% for the first two tests. The third test had a specificity of 98.9% for IgM and 94.4% for IgG. The fourth test had a specificity of 88.9% for IgM and 100% for IgG.Discussion COVID-19 serologic rapid tests are of variable specificity. Blood specimens from sentinel prenatal clinics provide an opportunity to validate serologic tests with population-based samples.

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COVID-19 diagnostics in context

Cited by 368 publications

References 20 publications

Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital

Clinical sensitivity and interpretation of PCR and serological COVID‐19 diagnostics for patients presenting to the hospital

A colorimetric RT-LAMP assay and LAMP-sequencing for detecting SARS-CoV-2 RNA in clinical samples

Using prenatal blood samples to validate COVID-19 rapid serologic tests

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