Systematic review with meta-analysis of diagnostic test accuracy for COVID-19 by mass spectrometry

Background: The global COVID-19 pandemic has led to extensive development in many fields, including the diag-nosis of COVID-19 infection by mass spectrometry. The aim of this systematic review and meta-analysis was to assess the accuracy of mass spectrometry diagnostic tests developed so far, across a wide range of biological ma-trices, and additionally to assess risks of bias and applicability in studies published to date. Method: 23 retrospective observational cohort studies were included in the systematic review using the PRISMA -DTA framework, with a total of 2858 COVID-19 positive participants and 2544 controls. Risks of bias and appli-cability were assessed via a QUADAS-2 questionnaire. A meta-analysis was also performed focusing on sensitiv -ity, specificity, diagnostic accuracy and Youden's Index, in addition to assessing heterogeneity. Findings: Sensitivity averaged 0.87 in the studies reviewed herein (interquartile range 0.81-0.96) and specificity 0.88 (interquartile range 0.82-0.98), with an area under the receiver operating characteristic summary curve of 0.93. By subgroup, the best diagnostic results were achieved by viral proteomic analyses of nasopharyngeal swabs and metabolomic analyses of plasma and serum. The performance of other sampling matrices (breath, sebum, sa -liva) was less good, indicating that these protocols are currently insufficiently mature for clinical application. Conclusions: This systematic review and meta-analysis demonstrates the potential for mass spectrometry and 'omics in achieving accurate test results for COVID-19 diagnosis, but also highlights the need for further work to optimize and harmonize practice across laboratories before these methods can be translated to clinical applications. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

This study aims to evaluate the accuracy of mass spectrometry diagnostic tests developed so far across various biological samples, with the best diagnostic results achieved by viral proteomic analyses of nasopharyngeal swabs and metabolomic analyses of plasma and serum. Other sampling matrices performed less well, indicating that these protocols are currently insufficiently mature for clinical application.