Diagnosis of SARS-Cov-2 infection using specimens other than naso- and oropharyngeal swabs: a systematic review and meta-analysis (preprint)

SUMMARY Background The rapid and accurate testing of SARS-CoV-2 infection is still crucial to mitigate, and eventually halt, the spread of this disease. Currently, nasopharyngeal swab (NPS) and oropharyngeal swab (OPS) are the recommended standard sampling, yet, with some limitations. Several specimens that are easier to collect are being tested as alternatives to nasal/throat swabs in nucleic acid assays for SARS-CoV-2 detection. This study aims to critically appraise and compare the clinical performance of RT-PCR tests using oral saliva, deep-throat saliva/ posterior oropharyngeal saliva (DTS/POS), sputum, urine, feces, and tears/conjunctival swab [CS]) against standard specimens (NPS, OPS, or a combination of both). Methods In this systematic review and meta-analysis, five databases (PubMed, Scopus, Web of Science, ClinicalTrial.gov and NIPH Clinical Trial) were searched up to the 30 th of December 2020. Case-control and cohort studies on the detection of SARS-CoV-2 were included. Methodological quality was assessed through the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2). Findings We identified 3022 entries, 33 of which (1.1%) met all required criteria and were included for the quantitative data analysis. Saliva presented the higher accuracy, 92.1% (95% CI: 70.0-98.3), with an estimated sensitivity of 83.9% (95% CI: 77.4-88.8) and specificity of 96.4% (95% CI: 89.5-98.8). DTS/POS samples had an overall accuracy of 79.7% (95% CI: 43.3-95.3), with an estimated sensitivity of 90.1% (95% CI: 83.3-96.9) and specificity of 63.1% (95% CI: 36.8-89.3). Remaining index specimens presented uncertainty given the lack of studies available. Interpretation Our meta-analysis shows that saliva samples from oral region provide a high sensitivity and specificity, being the best candidate as an alternative specimen to NPS/OPS for COVID-19 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial since DTS/POS samples may induce a higher rate of false positives. Urine, feces, tears/CS and sputum seem unreliable for diagnosis. Saliva testing may increase testing capacity, ultimately promoting the implementation of truly deployable COVID-19 tests, which could either work at the point-of-care (e.g. hospitals, clinics) or outbreak control spots (e.g. schools, airports, and nursing homes). Funding Nothing to declare. Research in context Evidence before this study The lack of systematized data on the accuracy performance of alternative specimens for the detection of SARS-CoV-2 (against the standard NPS/OPS). The ever-growing number of studies available, made this updated systematic review timely and of the utmost importance Added value of this study Our meta-analysis shows that saliva samples from the oral region provide a high sensitivity and specificity, being the best candidate as an alternative specimen to NPS/OPS for COVID-19 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial since DTS/POS samples may induce a higher rate of false positives. Implications of all the available evidence Saliva samples simply taken from the oral cavity are promising alternatives to the currently used nasal/throat swabs. Saliva specimens can be self-collected, mitigate the discomfort caused by sampling, reduce the transmission risk and increase testing capacity. Therefore, the validation of this alternative specimen will promote the implementation of truly deployable rapid tests for SARS-CoV-2 detection at the point-of-care or outbreak spots.

Diagnosis of SARS-CoV-2 Infection Using Specimens Other than Naso- and Oropharyngeal Swabs: A Systematic Review and Meta-Analysis (preprint)

Background: The rapid and accurate testing of SARS-CoV-2 infection is still crucial to mitigate, and eventually halt, the spread of this disease. Currently, nasopharyngeal swab (NPS) and oropharyngeal swab (OPS) are the recommended standard sampling, yet, with some limitations. Several specimens that are easier to collect are being tested as alternatives to nasal/throat swabs in nucleic acid assays for SARS-CoV-2 detection. This study aims to critically appraise and compare the clinical performance of RT-PCR tests using oral saliva, deep-throat saliva/ posterior oropharyngeal saliva (DTS/POS), sputum, urine, feces, and tears/conjunctival swab [CS]) against standard specimens (NPS, OPS, or a combination of both).Methods: In this systematic review and meta-analysis, five databases (PubMed, Scopus, Web of Science, ClinicalTrial.gov and NIPH Clinical Trial) were searched up to the 30th of December 2020. Case-control and cohort studies on the detection of SARS-CoV-2 were included. Methodological quality was assessed through the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS 2).Findings: We identified 3022 entries, 33 of which (1.1%) met all required criteria and were included for the quantitative data analysis. Saliva presented the higher accuracy, 92.1% (95% CI: 70.0-98.3), with an estimated sensitivity of 83.9% (95% CI: 77.4-88.8) and specificity of 96.4% (95% CI: 89.5-98.8). DTS/POS samples had an overall accuracy of 79.7% (95% CI: 43.3-95.3), with an estimated sensitivity of 90.1% (95% CI: 83.3-96.9) and specificity of 63.1% (95% CI: 36.8-89.3). Remaining index specimens presented uncertainty given the lack of studies available.Interpretation: Our meta-analysis shows that saliva samples from oral region provide a high sensitivity and specificity, being the best candidate as an alternative specimen to NPS/OPS for COVID-19 detection, with suitable protocols for swab-free sample collection to be determined and validated in the future. The distinction between oral and extra-oral salivary samples will be crucial since DTS/POS samples may induce a higher rate of false positives. Urine, feces, tears/CS and sputum seem unreliable for diagnosis. Saliva testing may increase testing capacity, ultimately promoting the implementation of truly deployable COVID-19 tests, which could either work at the point-of-care (e.g. hospitals, clinics) or outbreak control spots (e.g. schools, airports, and nursing homes).Funding Statement: This work was supported by national funds from FCT - Foundation for Science and Technology, I.P. through the CiiEM (project IDB/04585/2020), the Applied Molecular Biosciences Unit-UCIBIO (project UID/Multi/04378/2013), co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728) and the program Research4COVID 19 (Project nr. 662).Declaration of Interests: We declare no competing interests.

Predicting the evolution and control of COVID-19 pandemic in Portugal. (preprint)

The Coronavirus (COVID-19) is a world pandemic that has been affecting Portugal since 2 of March 2020. Portuguese government has been making efforts to contradict the exponential growth through social isolation measures. We have developed a mathematical model to predict the impact of such measures in the number of infected cases and peak of infection. We estimate the peak to be around 2 million infected cases by the beginning of May if no additional measures are taken. The model indicates that current measures effectively isolated 25-30% of the population, contributing for some reduction on the infection peak. Importantly, our simulations show that the infection burden can be further reduced with higher isolation degree, providing information for a second intervention.