SARS‐CoV2 antigen in whole mouth fluid may be a reliable rapid detection tool

Kannian, Priya; Lavanya, Chandra; Ravichandran, Krittika; Gita, Jayaraman Bagavad; Mahanathi, Pasuvaraj; Ashwini, Veeraraghavan; Kumarasamy, Nagalingeswaran; Rajan, Gunaseelan; Ranganathan, K; Challacombe, S. J.; Webster‐Cyriaque, Jennifer; Johnson, Newell W.

doi:10.1111/odi.13793

Cited by 10 publications

(7 citation statements)

References 10 publications

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“…All studies included were written in English, except for 3 in Spanish [57,66,138], 1 in Turkish [99], and 1 in French [157]. Out of the 194 studies, 26 conducted a case-control study [25,36,38,70,71,76,85,88,[92][93][94]97,98,100,107,112,139,144,148,149,155,160,170,172,186,188], while the remaining 168 were cross-sectional or cohort studies. The reference method was RT-PCR in all except 1 study, which used viral culture [139].…”

Section: Summary Of Studiesmentioning

confidence: 99%

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: An updated systematic review and meta-analysis with meta-regression analyzing influencing factors

et al. 2022

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Background Comprehensive information about the accuracy of antigen rapid diagnostic tests (Ag-RDTs) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is essential to guide public health decision makers in choosing the best tests and testing policies. In August 2021, we published a systematic review and meta-analysis about the accuracy of Ag-RDTs. We now update this work and analyze the factors influencing test sensitivity in further detail. Methods and findings We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched preprint and peer-reviewed databases for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 until August 31, 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity with reverse transcription polymerase chain reaction (RT-PCR) testing as a reference. To evaluate factors influencing test sensitivity, we performed 3 different analyses using multivariable mixed-effects meta-regression models. We included 194 studies with 221,878 Ag-RDTs performed. Overall, the pooled estimates of Ag-RDT sensitivity and specificity were 72.0% (95% confidence interval [CI] 69.8 to 74.2) and 98.9% (95% CI 98.6 to 99.1). When manufacturer instructions were followed, sensitivity increased to 76.3% (95% CI 73.7 to 78.7). Sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values (97.9% [95% CI 96.9 to 98.9] and 90.6% [95% CI 88.3 to 93.0] for Ct-values <20 and <25, compared to 54.4% [95% CI 47.3 to 61.5] and 18.7% [95% CI 13.9 to 23.4] for Ct-values ≥25 and ≥30) and was estimated to increase by 2.9 percentage points (95% CI 1.7 to 4.0) for every unit decrease in mean Ct-value when adjusting for testing procedure and patients’ symptom status. Concordantly, we found the mean Ct-value to be lower for true positive (22.2 [95% CI 21.5 to 22.8]) compared to false negative (30.4 [95% CI 29.7 to 31.1]) results. Testing in the first week from symptom onset resulted in substantially higher sensitivity (81.9% [95% CI 77.7 to 85.5]) compared to testing after 1 week (51.8%, 95% CI 41.5 to 61.9). Similarly, sensitivity was higher in symptomatic (76.2% [95% CI 73.3 to 78.9]) compared to asymptomatic (56.8% [95% CI 50.9 to 62.4]) persons. However, both effects were mainly driven by the Ct-value of the sample. With regards to sample type, highest sensitivity was found for nasopharyngeal (NP) and combined NP/oropharyngeal samples (70.8% [95% CI 68.3 to 73.2]), as well as in anterior nasal/mid-turbinate samples (77.3% [95% CI 73.0 to 81.0]). Our analysis was limited by the included studies’ heterogeneity in viral load assessment and sample origination. Conclusions Ag-RDTs detect most of the individuals infected with SARS-CoV-2, and almost all (>90%) when high viral loads are present. With viral load, as estimated by Ct-value, being the most influential factor on their sensitivity, they are especially useful to detect persons with high viral load who are most likely to transmit the virus. To further quantify the effects of other factors influencing test sensitivity, standardization of clinical accuracy studies and access to patient level Ct-values and duration of symptoms are needed.

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Section: Summary Of Studiesmentioning

confidence: 99%

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: An updated systematic review and meta-analysis with meta-regression analyzing influencing factors

et al. 2022

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“…This is consistent with in vitro cell culture and RT-PCR studies that have shown reduction in SARS-CoV2 burden. 2,3,5,6 We also demonstrated for the first time that RAT is superior to RT-PCR for determining the efficacy of interventions designed to decrease oral transmission. The unbiased detection of viral RNA by RT-PCR irrespective of active viral infection can be problematic.…”

Section: Discussionmentioning

confidence: 85%

Povidone iodine, hydrogen peroxide and chlorhexidine mouthwashes reduce SARS-CoV2 burden in whole mouth fluid and respiratory droplets

Bg¹,

Rajan²,

Kannian

et al. 2021

Preprint

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SARS-CoV2 is transmitted primarily through oral mouth secretions and respiratory droplets. Commercial mouthwashes, povidone iodine (PI), hydrogen peroxide (HP) and chlorhexidine (CHX) have been tested in cell culture and RT-PCR studies for their efficacy to reduce SARS-CoV2 burden. Here, we evaluated SARS-CoV2 burden in whole mouth fluid (WMF) and respiratory droplets (RD) samples before and after the use of PI, HP or CHX mouthwashes in hospitalized COVID-19 patients using RT-PCR and rapid antigen test (RAT). Thirty-six SARS-CoV2 RT-PCR-positive in-patients were randomly assigned to one of the four groups: 20 and 60 minutes after 1% w/v PI or 1.5% HP; 90 and 180 minutes after 1.5% HP or 0.2% w/v CHX. WMF and RD samples were collected concurrently at baseline and after the two different time points. RD (92%) showed a higher reduction in SARS-CoV2 burden than WMF samples (50%; p=0.008). SARS-CoV2 burden was statistically lower at both 20 minutes (p=0.02) and 60 minutes (p=0.03) with PI; at 20 minutes with HP (p=0.0001); and 90 minutes with CHX (p=0.04). The overall and individual mean logarithmic reductions in the WMF and RD samples were greater than 1.0 at 20, 60 and 90 minutes after PI, HP or CHX. RAT-positive patients at 90 minutes post-treatment (n=3) demonstrated a one log increase in virus copies. Among the three RAT-negative post-treatment patients, SARS-CoV2 burden declined by one log in two while the third patient had a slight increase in RNA copies. In conclusion, we have shown for the first time that the mouthwashes, PI, HP and CHX can reduce the SARS-CoV2 burden in the concurrently collected RD and WMF samples. RAT is more appropriate than RT-PCR to evaluate the efficacy of the mouthwashes.

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“…All studies were written in English, except for 3 in Spanish [53, 62, 134], 1 in Turkish [95], and 1 in French [153]. Out of the 196 studies, 26 conducted a case-control study [21, 32, 34, 66, 67, 72, 81, 84, 88-90, 93, 94, 96, 103, 108, 135, 140, 144, 145, 151, 156, 166, 168, 182, 184], while the remaining 168 were cross-sectional or cohort studies. The reference method was RT-PCR in all except 1 study, which used viral culture [135].…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, saliva swabs (4 data sets, 1,216 samples) showed the lowest pooled sensitivity with only 50.1% (95% CI 7.7 to 92.3) (Fig 3c). In 3 of the data sets utilizing a saliva sample, saliva was collected as whole mouth fluid [20, 88, 150]. The fourth used a cheek swab for sample collection [51].…”

Section: Resultsmentioning

confidence: 99%

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: an updated systematic review and meta-analysis with meta regression analyzing influencing factors

Brümmer

Katzenschlager

McGrath

et al. 2022

Preprint

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Background Comprehensive information about the accuracy of antigen rapid diagnostic tests (Ag-RDTs) for SARS-CoV-2 is essential to guide public health decision makers in choosing the best tests and testing policies. In August 2021, we published a systematic review and meta-analysis about the accuracy of Ag-RDTs. We now update this work and analyze the factors influencing test sensitivity in further detail. Methods and findings We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 until August 31, 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity with reverse transcription polymerase chain reaction (RT-PCR) testing as a reference. To evaluate factors influencing test sensitivity, we performed 3 different analyses using multivariate mixed-effects meta-regression models. We included 194 studies with 221,878 Ag-RDTs performed. Overall, the pooled estimates of Ag-RDT sensitivity and specificity were 72.0% (95% confidence interval [CI] 69.8 to 74.2) and 98.9% (95% CI 98.6 to 99.1), respectively. When manufacturer instructions were followed, sensitivity increased to 76.4% (95%CI 73.8 to 78.8). Sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values (sensitivity of 97.9% [95% CI 96.9 to 98.9] and 90.6% [95% CI 88.3 to 93.0] for Ct-values <20 and <25, compared to 54.4% [95% CI 47.3 to 61.5] and 18.7% [95% CI 13.9 to 23.4] for Ct-values ≥25 and ≥30) and was estimated to increase by 2.9 percentage points (95% CI 1.7 to 4.0) for every unit decrease in mean Ct-value when adjusting for testing procedure and patients symptom status. Concordantly, we found the mean Ct-value to be lower for true positive (22.2 [95% CI 21.5 to 22.8]) compared to false negative (30.4 [95% CI 29.7 to 31.1]) results. Testing in the first week from symptom onset resulted in substantially higher sensitivity (81.9% [95% CI 77.7 to 85.5]) compared to testing after 1 week (51.8%, 95% CI 41.5 to 61.9). Similarly, sensitivity was higher in symptomatic (76.2% [95% CI 73.3 to 78.9]) compared to asymptomatic (56.8% [95% CI 50.9 to 62.4]) persons. However, both effects were mainly driven by the Ct-value of the sample. With regards to sample type, highest sensitivity was found for nasopharyngeal (NP) and combined NP/oropharyngeal samples (70.8% [95% CI 68.3 to 73.2]), as well as in anterior nasal/mid-turbinate samples (77.3% [95% CI 73.0 to 81.0]). Conclusion Ag-RDTs detect most of the individuals infected with SARS-CoV-2, and almost all when high viral loads are present (>90%). With viral load, as estimated by Ct-value, being the most influential factor on their sensitivity, they are especially useful to detect persons with high viral load who are most likely to transmit the virus. To further quantify the effects of other factors influencing test sensitivity, standardization of clinical accuracy studies and access to patient level Ct-values and duration of symptoms are needed.

show abstract

SARS‐CoV2 antigen in whole mouth fluid may be a reliable rapid detection tool

Cited by 10 publications

References 10 publications

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: An updated systematic review and meta-analysis with meta-regression analyzing influencing factors

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: An updated systematic review and meta-analysis with meta-regression analyzing influencing factors

Povidone iodine, hydrogen peroxide and chlorhexidine mouthwashes reduce SARS-CoV2 burden in whole mouth fluid and respiratory droplets

Accuracy of rapid point-of-care antigen-based diagnostics for SARS-CoV-2: an updated systematic review and meta-analysis with meta regression analyzing influencing factors

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