False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications

Woloshin, Steven; Patel, Neeraj G; Kesselheim, Aaron S.

doi:10.1056/nejmp2015897

Cited by 809 publications

(810 citation statements)

References 2 publications

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“…We tried to fulfill the ideal requirements relevant to validate a diagnostic test 22 . The 12 patients selected to scent-train the dogs provided a variety of sources, timing, and disease severity that included many of the real-life situations present in COVID-19 (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Dog Savior: Immediate Scent-Detection of SARS-COV-2 by Trained Dogs

Vesga

Valencia

Mira

et al. 2020

Preprint

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Molecular tests for viral diagnostics are essential to confront the COVID-19 pandemic, but their production and distribution cannot satisfy the current high demand. Early identification of infected people and their contacts is the key to being able to isolate them and prevent the dissemination of the pathogen; unfortunately, most countries are unable to do this due to the lack of diagnostic tools. Dogs can identify, with a high rate of precision, unique odors of volatile organic compounds generated during an infection; as a result, dogs can diagnose infectious agents by smelling specimens and, sometimes, the body of an infected individual. We trained six dogs of three different breeds to detect SARS-CoV-2 in respiratory secretions of infected patients and evaluated their performance experimentally, comparing it against the gold standard (rRT-PCR). Here we show that viral detection takes one second per specimen. After scent-interrogating 9,200 samples, our six dogs achieved independently and as a group very high sensitivity, specificity, predictive values, accuracy, and likelihood ratio, with very narrow confidence intervals. The highest metric was the negative predictive value, indicating that with a disease prevalence of 7.6%, 99.9% of the specimens indicated as negative by the dogs did not carry the virus. These findings demonstrate that dogs could be useful to track viral infection in humans, allowing COVID-19 free people to return to work safely. OV came up with the idea, obtained the funding, designed and supervised the training and the experimental process, and wrote the manuscript.AFV directed the training process and supervised the dog experiments in the field. AM, FO and EO trained the dogs and participated in all the experiments with them.

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Section: Discussionmentioning

confidence: 99%

Dog Savior: Immediate Scent-Detection of SARS-COV-2 by Trained Dogs

Vesga

Valencia

Mira

et al. 2020

Preprint

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“…21 Understanding the predictive value of NAAT with regard to time from exposure and symptom onset is important as the assay may not have been appropriately validated against a clinically meaningful reference standard for detecting SARS-CoV-2 in the absence of symptoms (during earlier stages of the disease) or in asymptomatic individuals. 22 The sensitivity of a test must be high for adequate containment measures and assessment of clinical sensitivity in asymptomatic patients is warranted.…”

Section: Assay Performance and Limitationsmentioning

confidence: 99%

COVID‐19 Clinical Diagnostics and Testing Technology

2020

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Given the global nature of the coronavirus disease 2019 (COVID‐19) pandemic, the need for disease detection and expanding testing capacity remains critical priorities. This review discusses the technological advances in testing capability and methodology that are currently used or in development for detecting the novel coronavirus. We describe the current clinical diagnostics and technology, including molecular and serological testing approaches, for severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) testing as well as address their advantages and limitations. Nucleic acid amplification technology for molecular diagnostics remains the gold standard for virus detection. We highlight alternative molecular detection techniques used for developing novel COVID‐19 diagnostics on the horizon. Antibody response against SARS‐CoV‐2 remains poorly understood and proper validation of serology tests is necessary to demonstrate their accuracy and clinical utility. In order to bring the pandemic under control, we must speed up the development of rapid and widespread testing through improvements in clinical diagnostics and testing technology as well as access to these tools.

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“…full spike, nucleocapsid) will permit to extend our initial observations on RBD antibodies to a broader humoral response to SARS-CoV-2 and help to better define its persistence. Nevertheless, the availability of sequential samples from the CCP repeated donors permitted to better pinpoint the time at which the anti-RBD response starts to significantly decline, regardless of the initial anti-RBD antibody level which has been shown to correlate with disease severity (19,26,27).…”

Section: Main Textmentioning

confidence: 99%

Longitudinal analysis of the humoral response to SARS-CoV-2 spike RBD in convalescent plasma donors

Perreault

Tremblay

Fournier

et al. 2020

Preprint

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Héma-Québec, the blood supplier in the Province of Quebec, Canada, collects and tests convalescent plasma used in a clinical trial to determine the clinical efficacy of this product for the treatment of hospitalized COVID-19 patients. So far, we have collected 1159 plasma units from 282 COVID-19 convalescent donors. The presence of antibodies to the receptor binding domain (RBD) of SARS-CoV-2 spike protein in convalescent donors was established at the first donation. Seropositive donors were asked to donate additional plasma units every six days. Until now, 15 donors have donated at least four times and, in some cases, up to nine times. This allowed us to perform a longitudinal analysis of the persistence of SARS-CoV-2 RBD-specific antibodies in these repeat donors, with the first donation occurring 33-77 days after symptoms onset and donations up to 71-114 days after symptoms onset thereafter. In all donors, the level of antibodies remained relatively stable up to about 76 days after symptoms onset but then started to decrease more rapidly to reach, in some convalescent donors, a seronegative status within 100-110 days after symptoms onset. The decline in anti-RBD antibodies was not related to the number of donations but strongly correlated with the numbers of days after symptoms onset (r = 0.821). This suggests that de novo secretion of SARS-CoV-2 RBD antibodies by short-lived plasma cells stopped about 2-3 months after disease onset, an observation that has important implications for convalescent plasma collection and seroprevalence studies undertaken several months after the peak of infection.

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False Negative Tests for SARS-CoV-2 Infection — Challenges and Implications

Cited by 809 publications

References 2 publications

Dog Savior: Immediate Scent-Detection of SARS-COV-2 by Trained Dogs

Dog Savior: Immediate Scent-Detection of SARS-COV-2 by Trained Dogs

COVID‐19 Clinical Diagnostics and Testing Technology

Longitudinal analysis of the humoral response to SARS-CoV-2 spike RBD in convalescent plasma donors

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