SARS-CoV-2 Viral Load Predicts COVID-19 Mortality

Pujadas, Elisabet; Chaudhry, Fayzan; McBride, Russell; Richter, Felix; Zhao, Shan; Wajnberg, Ania; Nadkarni, Girish N.; Glicksberg, Benjamin S.; Houldsworth, Jane; Cordon‐Cardo, Carlos

doi:10.1101/2020.06.11.20128934

Cited by 86 publications

(100 citation statements)

References 6 publications

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“…A higher clinical sensitivity would be expected when only hospitalized patients were tested. 30 For Bioeasy, our point estimate of specificity falls within the confidence interval of specificity of the only other independently published study, which had few RT-PCR negative cases. 14 Overall, our study had several strengths.…”

Section: Figure 1 Study Flowsupporting

confidence: 70%

Evaluation of the accuracy, ease of use and limit of detection of novel, rapid, antigen-detecting point-of-care diagnostics for SARS-CoV-2

Krüger

Gaeddert

Koeppel

et al. 2020

Preprint

112

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Background: Reliable point-of-care (POC) diagnostics not requiring laboratory infrastructure could be a game changer in the COVID-19 pandemic, particularly in the Global South. We assessed performance, limit of detection (LOD) and ease-of-use of three antigen-detecting, rapid POC diagnostics (Ag-RDT) for SARS-CoV-2. Methods: This prospective, multi-centre diagnostic accuracy study, recruited participants suspected to have SARS-CoV2 in Germany and UK. Paired nasopharyngeal swabs (NP) or NP and/or oropharyngeal swabs (OP) were collected from participants (one for clinical real-time reverse transcription polymerase chain reaction (RT-PCR) and one for Ag-RDT testing). Performance of each of three Ag-RDTs was compared to RT-PCR overall, and according to predefined subcategories e.g. cycle threshold (CT)-value, days from symptom onset, etc. In addition, limited verification of analytical limit-of-detection (LOD) was determined. To understand the usability of each Ag-RDT a System Usability Scale (SUS) questionnaire and ease-of-use assessment were performed. Results: Between April 17th and August 25th, 2020, 2417 participants were enrolled, with 70 (3.0%) testing positive by RT-PCR. The best-performing test (SD Biosensor, Inc. STANDARD Q) was 76.6% [95% Confidence Interval (CI) 62.8-86.4] sensitive and 99.3% [CI 98.6-99.6] specific. A sub-analysis showed all samples with RT-PCR CT-values <25 were detectable by STANDARD Q. The test was considered easy-to-use (SUS 86/100) and suitable for POC. Bioeasy and Coris showed specificity of 93.1% [CI 91.0%-94.8%] and 95.8% [CI 93.4%-97.4%], respectively, not meeting the predefined target of ≥98%. Conclusion: There is large variability in performance of Ag-RDT tests with one test showing promise. Given the usability at POC, these tests are likely to have impact despite imperfect sensitivity; however further research and modelling are needed.

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Section: Figure 1 Study Flowsupporting

confidence: 70%

Evaluation of the accuracy, ease of use and limit of detection of novel, rapid, antigen-detecting point-of-care diagnostics for SARS-CoV-2

Krüger

Gaeddert

Koeppel

et al. 2020

Preprint

112

View full text Add to dashboard Cite

show abstract

“…For example, a study performed on 3,303 patients who tested positive for SARS-CoV-2 estimated the viral load to be in the range of 1 copy per μL to 10 8 copies per μL, with the majority of the samples in the range of 10 4 to 10 8 copies per μL (42). In another study with 1,145 hospitalized SARS-CoV-2 positive patients (average age of 64.6 y), the median viral load was 1,440 viral copies per μL (43). These viral loads can easily be measured using our POC device.…”

Section: Discussionmentioning

confidence: 97%

Rapid isothermal amplification and portable detection system for SARS-CoV-2

Ganguli

Mostafa

Berger

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

324

287

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The COVID-19 pandemic provides an urgent example where a gap exists between availability of state-of-the-art diagnostics and current needs. As assay protocols and primer sequences become widely known, many laboratories perform diagnostic tests using methods such as RT-PCR or reverse transcription loop mediated isothermal amplification (RT-LAMP). Here, we report an RT-LAMP isothermal assay for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and demonstrate the assay on clinical samples using a simple and accessible point-of-care (POC) instrument. We characterized the assay by dipping swabs into synthetic nasal fluid spiked with the virus, moving the swab to viral transport medium (VTM), and sampling a volume of the VTM to perform the RT-LAMP assay without an RNA extraction kit. The assay has a limit of detection (LOD) of 50 RNA copies per μL in the VTM solution within 30 min. We further demonstrate our assay by detecting SARS-CoV-2 viruses from 20 clinical samples. Finally, we demonstrate a portable and real-time POC device to detect SARS-CoV-2 from VTM samples using an additively manufactured three-dimensional cartridge and a smartphone-based reader. The POC system was tested using 10 clinical samples, and was able to detect SARS-CoV-2 from these clinical samples by distinguishing positive samples from negative samples after 30 min. The POC tests are in complete agreement with RT-PCR controls. This work demonstrates an alternative pathway for SARS-CoV-2 diagnostics that does not require conventional laboratory infrastructure, in settings where diagnosis is required at the point of sample collection.

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“…A steroid, dexamethasone, that dampens inflammatory responses, has shown clinical benefit in ventilated patients in the RECOVERY trial (21). Some reports suggested that high viral loads are associated with a higher risk of disease severity and a higher rate of mortality in adults (22)(23)(24), while others found that viral load is higher in children than in adults (25). Quantifying the viral dynamics in the LRT will help to better understand these issues.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of SARS-CoV-2 infection in the human upper and lower respiratory tracts and their relationship with infectiousness

Zitzmann

Ribeiro

et al. 2020

Preprint

161

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SARS-CoV-2 is a human pathogen that causes infection in both the upper respiratory tract (URT) and the lower respiratory tract (LRT). The viral kinetics of SARS-CoV-2 infection and how they relate to infectiousness and disease progression are not well understood. Here, we develop data-driven viral dynamic models of SARS-CoV-2 infection in both the URT and LRT. We fit the models to viral load data from patients with likely infection dates known, we estimated that infected individuals with a longer incubation period had lower rates of viral growth, took longer to reach peak viremia in the URT, and had higher chances of presymptomatic transmission. We then developed a model linking viral load to infectiousness. We found that to explain the substantial fraction of transmissions occurring presymptomatically, the infectiousness of a person should depend on a saturating function of the viral load, making the logarithm of the URT viral load a better surrogate of infectiousness than the viral load itself. Comparing the roles of target-cell limitation, the innate immune response, proliferation of target cells and spatial infection in the LRT, we found that spatial dissemination in the lungs is likely to be an important process in sustaining the prolonged high viral loads. Overall, our models provide a quantitative framework for predicting how SARS-CoV-2 within-host dynamics determine infectiousness and represent a step towards quantifying how viral load dynamics and the immune responses determine disease severity.

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SARS-CoV-2 Viral Load Predicts COVID-19 Mortality

Cited by 86 publications

References 6 publications

Evaluation of the accuracy, ease of use and limit of detection of novel, rapid, antigen-detecting point-of-care diagnostics for SARS-CoV-2

Evaluation of the accuracy, ease of use and limit of detection of novel, rapid, antigen-detecting point-of-care diagnostics for SARS-CoV-2

Rapid isothermal amplification and portable detection system for SARS-CoV-2

Kinetics of SARS-CoV-2 infection in the human upper and lower respiratory tracts and their relationship with infectiousness

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