TABLE 2.

COVID-19 testing by mass-spectrometry.

Specimen	No of patients	Reference method	Specimen preprocessing	Target	*MS approach	Results	References
NPS, OPS	985	RT-qPCR	Ethanol precipitation, lysis, trypsin digestion; automated magnetic bead-based preparation	Nucleoprotein	TFC-MS/MS	Sensitivity: 84% Specificity: 97%	Cardozo et al., 2020
NPS	362	RT-qPCR	No preprocessing required, 1:1 mixing with matrix solution	Untargeted	MALDI-TOF MS; machine learning – SVM	Accuracy: 93.9%) FP: 7%, FN: 5%	Nachtigall et al., 2020
Gargle solution	3	RT-qPCR	Acetone precipitation, tryptic digestion	Nucleoprotein	LC-MS	SARS-CoV-2 nucleoprotein identified in 2 of the three samples	Ihling et al., 2020
NPS	8	RT-qPCR	Heating, isopropanol precipitation, tryptic digestion	Nucleoprotein	LC-MS/MS	N protein detection in SARS-CoV-2 positive samples	Nikolaev et al., 2020
NPS	311	RT-qPCR	No preprocessing required, 1 μl specimen mixed with 1 μl matrix solution	Untargeted	MALDI-TOF MS; Multivariate analysis	Accuracy:67.66%, Sensitivity:61.76%, Specificity:71.72%	Rocca et al., 2020
NPS, OPS	103	RT-qPCR	Lysis, TCA precipitation	Spike, replicase	LC-MS/MS	Sensitivity: 90.5% Specificity: 100%	Singh et al., 2020
Serum	298	RT-qPCR	Dilution, 1:1 mixing with matrix solution	Untargeted	MALDI-TOF MS; machine learning – logistic regression	Accuracy: 99% Sensitivity: 98% Specificity: 100%	Yan et al., 2021
NPS	199	RT-qPCR	No preprocessing required, 1:1 mixing with matrix solution	Untargeted	MALDI-TOF MS; machine learning –	Accuracy: 98.3%, PPA:100% NPA: 96%	Tran et al., 2021
NPS	16	RT-qPCR	Heat inactivation, denaturation, tryptic digestion	Nucleoprotein, spike	LC-MS/MS	94% concordance	Schuster et al., 2021
NPS	237	RT-qPCR	Virus inactivation with guanidine thiocyanate, dilution, 1:1 mixing with matrix solution	Untargeted	MALDI-TOF MS; machine learning	Accuracy, sensitivity and specificity: >90%	Deulofeu et al., 2021
Plasma	815	RT-qPCR	Dilution, homogenization, centrifugation, formic acid ionization	Untargeted	HESI-MS; machine learning	Sensitivity > 83% Specificity > 96%	Delafiori et al., 2021

RT-qPCR, reverse transcriptase quantitative polymerase chain reaction; NPS, nasopharyngeal swab; OPS, oropharyngeal swab; TCA, trichloroacetic acid; TFC-MS/MS, turbulent flow chromatography coupled to tandem mass spectrometry; MALDI-TOF MS, matrix assisted laser desorption ionization-time of flight mass spectrometry; LC-MS, liquid chromatography mass spectrometry; LC-MS/MS, liquid chromatography-tandem mass spectrometry; FP, false positive; FN, false negative; PPA, positive percent agreement; NPA, negative percent agreement; SVM, support vector machine; HESI-MS, heated electrospray ionization – mass spectrometry. * Studies with nucleic acid amplification tests (NAAT) based on mass spectrometry were excluded.