Volatile organic components as Covid-19 biomarkers: a systematic review


  • Lucas Vinnicio de Araújo Santana
  • Marcelo Weinstein Teixeira
  • Mariza Brandão Palma
  • Anísio Francisco Soares




systematic review, Covid-19 pandemics, volatile organic compounds, trained dogs, health approach


In March 2020, the WHO declared the novel Coronavirus pandemic with 118,000 cases, 4.2 thousand deaths, and 114 affected countries. Amidst the absence of effective treatments and vaccines, scientists focused on diagnosing and preventing transmission. Pathogenic agent infections induce cellular behavior changes, crucial for developing diagnostic techniques. A systematic review, following PRISMA guidelines, investigated COVID-19 and volatile organic compound (VOC) biomarkers. From 35 selected articles, two main VOC detection approaches emerged: trained dogs and chemical-analytical tools with artificial intelligence. VOC detection proved comparable to the gold standard PCR test for COVID-19 diagnosis. While not a replacement, VOC detection complements PCR testing, offering a unique health approach. Overall, the review highlights the efficacy of VOC detection, especially in areas with limited PCR access. However, these techniques should supplement other preventive measures like mask-wearing, social distancing, and hand hygiene.


ANGELETTI, S. et al. COVID‐19 sniffer dog experimental training: Which protocol and which implications for reliable sidentification? Journal of Medical Virology, 26 jun. 2021.

BERNA, A. Z. et al. Reproducible Breath Metabolite Changes in Children with SARS-CoV-2 Infection. ACS Infectious Diseases, v. 7, n. 9, p. 2596–2603, 28 jul. 2021.

BERNA, A. Z.; JOHN, A. R. O. Breath Metabolites to Diagnose Infection. Disponível em:<https://pubmed.ncbi.nlm.nih.gov/34969107/>. Acesso em: fev. 3DC.

CATALA, A. et al. Dogs demonstrate the existence of an epileptic seizure odour in humans. Scientific Reports, v. 9, n. 1, p. 4103, 28 mar. 2019.

CHABER, A. et al. Evaluation of canine detection of COVID‐19 infected individuals under controlled settings. Transboundary and Emerging Diseases, v. 69, n. 5, 5 abr. 2022.

CHEN, H. et al. COVID-19 screening using breath-borne volatile organic compounds. Journal of Breath Research, 8 out. 2021.

CORNU, J.-N. et al. Olfactory Detection of Prostate Cancer by Dogs Sniffing Urine: A Step Forward in Early Diagnosis. European Urology, v. 59, n. 2, p. 197–201, fev. 2011.

CRESPO-CAJIGAS, J. et al. Investigating the Use of SARS-CoV-2 (COVID-19) Odor Expression as a Non-Invasive Diagnostic Tool—Pilot Study. Diagnostics, v. 13, n. 4, p. 707, 13 fev. 2023.

DE ALMEIDA, M. B. et al. Clinical trial and detection of SARS-CoV-2 by a commercial breath analysis test based on Terahertz technology. PLOS ONE, v. 17, n. 9, p. e0273506, 20 set. 2022.

DE VRIES, R. et al. Ruling out SARS-CoV-2 infection using exhaled breath analysis by electronic nose in a public health setting. 16 fev. 2021.

EHMANN, R. et al. Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon. European Respiratory Journal, v. 39, n. 3, p. 669–676, 18 ago. 2011.

ESSLER, J. L. et al. Discrimination of SARS-CoV-2 infected patient samples by detection dogs: A proof of concept study. PLOS ONE, v. 16, n. 4, p. e0250158, 14 abr. 2021.

FEUERHERD, M. et al. A proof of concept study for the differentiation of SARS-CoV-2, hCoV-NL63, and IAV-H1N1 in vitro cultures using ion mobility spectrometry. Scientific Reports, v. 11, n. 1, 11 out. 2021.

GENGLER, I. et al. Sinonasal pathophysiology of SARS‐CoV ‐2 and COVID ‐19: A systematic review of the current evidence. Laryngoscope Investigative Otolaryngology, 16 abr. 2020.

GOKOOL, V. A. et al. The Use of Biological Sensors and Instrumental Analysis to Discriminate COVID-19 Odor Signatures. Biosensors, v. 12, n. 11, p. 1003, 11 nov. 2022.

GRANDJEAN, D. et al. Screening for SARS-CoV-2 persistence in Long COVID patients using sniffer dogs and scents from axillary sweats samples. 12 jan. 2022.

GRASSIN-DELYLE, S. et al. Metabolomics of exhaled breath in critically ill COVID-19 patients: A pilot study. EBioMedicine, v. 63, p. 103154, jan. 2021.

HASAN, M. R.; SULEIMAN, M.; PÉREZ-LÓPEZ, A. Metabolomics in the Diagnosis and Prognosis of COVID-19. Frontiers in Genetics, v. 12, 23 jul. 2021.

HORVATH, G.; ANDERSSON, H.; NEMES, S. Cancer odor in the blood of ovarian cancer patients: a retrospective study of detection by dogs during treatment, 3 and 6 months afterward. BMC Cancer, v. 13, n. 1, 26 ago. 2013.

JENDRNY, P. et al. Scent dog identification of SARS-CoV-2 infections in different body fluids. BMC Infectious Diseases, v. 21, n. 1, 27 jul. 2021.

MAA, E. et al. Canine detection of volatile organic compounds unique to human epileptic seizure. Epilepsy & Behavior, v. 115, p. 107690, fev. 2021.

KWIATKOWSKI, A. et al. Clinical studies of detecting COVID-19 from exhaled breath with electronic nose. Scientific Reports, v. 12, n. 1, 26 set. 2022.

LAI, C. K. et al. Detection of volatile organic compounds in exhaled breath for mass screening of COVID-19 infection. Hong Kong Medical Journal, 17 dez. 2022.

LEONG, S. X. et al. Noninvasive and Point-of-Care Surface-Enhanced Raman Scattering (SERS)-Based Breathalyzer for Mass Screening of Coronavirus Disease 2019 (COVID-19) under 5 min. ACS Nano, v. 16, n. 2, p. 2629–2639, 18 jan. 2022.

MAIA, R. DE C. C. et al. Canine Olfactory Detection of SARS-COV2-Infected Patients: A One Health Approach. Frontiers in Public Health, v. 9, 21 out. 2021.

MANCILLA-TAPIA, J. M. et al. Dogs Detecting COVID-19 From Sweat and Saliva of Positive People: A Field Experience in Mexico. Frontiers in Medicine, v. 9, 1 abr. 2022.

MANGALMURTI, N.; HUNTER, C. A. Cytokine Storms: Understanding COVID-19. Immunity, v. 53, n. 1, p. 19–25, jul. 2020.

MAURER, M. et al. Detection of Bacteriuria by Canine Olfaction. Open Forum Infectious Diseases, v. 3, n. 2, 2016.

MAYI, B. S. et al. The role of Neuropilin-1 in COVID-19. PLoS Pathog, p. e1009153–e1009153, 2021.

MENDEL, J. et al. Preliminary accuracy of COVID-19 odor detection by canines and HS-SPME-GC-MS using exhaled breath samples. Forensic Science International: Synergy, v. 3, p. 100155, 2021.

MUTESA, L. et al. Use of trained scent dogs for detection of COVID-19 and evidence of cost-saving. Frontiers in Medicine, v. 9, 1 dez. 2022.

OMS afirma que COVID-19 é agora caracterizada como pandemia - OPAS/OMS | Organização Pan-Americana da Saúde. Disponível em: <https://www.paho.org/pt/news/11-3-2020-who-characterizes-covid-19-pandemic>.

NAZARETH, J. et al. Discriminatory Ability of Gas Chromatography-Ion Mobility Spectrometry to Identify Patients Hospitalized With COVID-19 and Predict Prognosis. Open Forum Infectious Diseases, v. 9, n. 11, p. ofac509, 1 nov. 2022.

RODRÍGUEZ-AGUILAR, M. et al. Comparative analysis of chemical breath-prints through olfactory technology for the discrimination between SARS-CoV-2 infected patients and controls. Clinica Chimica Acta, v. 519, p. 126–132, ago. 2021.

RUSZKIEWICZ, D. et al. Diagnosis of COVID-19 by Analysis of Breath with Gas Chromatography-Ion Mobility Spectrometry: A Feasibility Study. SSRN Electronic Journal, 2020.

SARKIS, R. et al. New method of screening for COVID-19 disease using sniffer dogs and scents from axillary sweat samples. Journal of Public Health, v. 44, n. 1, p. e36–e41, 23 jun. 2021.

SAVITZ, J. The kynurenine pathway: a finger in every pie. Molecular Psychiatry, v. 25, n. 1, p. 131–147, 12 abr. 2019.

SHARMA, R. et al. Portable Breath-Based Volatile Organic Compound Monitoring for the Detection of COVID-19 During the Circulation of the SARS-CoV-2 Delta Variant and the Transition to the SARS-CoV-2 Omicron Variant. JAMA Network Open, v. 6, n. 2, p. e230982, 28 fev. 2023.

SHLOMO, I. B. et al. Detection of SARS-CoV-2 infection by exhaled breath spectral analysis: Introducing a ready-to-use point-of-care mass screening method. eClinicalMedicine, v. 45, p. 101308, mar. 2022.

SINGLETARY, M. et al. A Novel Method for Training the Interdiction of Restricted and Hazardous Biological Materials by Detection Dogs. Frontiers in Medicine, v. 9, 12 abr. 2022.

SNITZ, K. et al. Proof of concept for real-time detection of SARS CoV-2 infection with an electronic nose. PLOS ONE, v. 16, n. 6, p. e0252121, 2 jun. 2021.

SONODA, H. et al. Colorectal cancer screening with odour material by canine scent detection. Gut, v. 60, n. 6, p. 814–819, 31 jan. 2011.

SUN, P. et al. Understanding of COVID-19 based on current evidence. Journal of Medical Virology, v. 92, n. 6, 25 fev. 2020.

The enemy within: How SARS-CoV-2 uses our own proteins to infect our cells. Disponível em: <https://www.cas.org/resources/cas-insights/drug-discovery/covid-19-spike-protein>.

TWELE, F. et al. Detection of Post-COVID-19 Patients Using Medical Scent Detection Dogs—A Pilot Study. Frontiers in Medicine, v. 9, 16 jun. 2022.

VALLEJO DEGAUDENZI, A. et al. SARS-CoV-2 Breath Tests Implementation for the Rapid COVID-19 Surveillance: A Game Changer?- A Review of Existing Data. InterAmerican Journal of Medicine and Health, v. 4, p. 1–6, 23 mar. 2022.

WINTJENS, A. G. W. E. et al. Applying the electronic nose for pre-operative SARS-CoV-2 screening. Surgical Endoscopy, v. 35, n. 12, p. 6671–6678, 2 dez. 2020.

WOOLLAM, M. et al. Exhaled VOCs can discriminate subjects with COVID-19 from healthy controls. Journal of Breath Research, 22 abr. 2022.

WOROBEY, M. et al. The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic. Science, v. 377, n. 6609, 26 jul. 2022.

XIAO, N. et al. Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications. Nature Communications, v. 12, n. 1, 12 mar. 2021.

XUE, C. et al. Intelligent COVID-19 screening platform based on breath analysis. Journal of Breath Research, v. 17, n. 1, p. 016005, 24 nov. 2022.

ZAMORA-MENDOZA, B. N. et al. Chemometric analysis of the global pattern of volatile organic compounds in the exhaled breath of patients with COVID-19, post-COVID and healthy subjects. Proof of concept for post-COVID assessment. Talanta, v. 236, p. 122832, jan. 2022.

ZAMORA-MENDOZA, B. N. et al. Determination of global chemical patterns in exhaled breath for the discrimination of lung damage in postCOVID patients using olfactory technology. Talanta, v. 256, p. 124299, maio 2023.

ZHANG, P. et al. A feasibility study of Covid-19 detection using breath analysis by high-pressure photon ionization time-of-flight mass spectrometry. Journal of Breath Research, v. 16, n. 4, p. 046009, 12 set. 2022.



How to Cite

Santana, L. V. de A., Teixeira, M. W., Palma, M. B., & Soares, A. F. (2024). Volatile organic components as Covid-19 biomarkers: a systematic review. OBSERVATÓRIO DE LA ECONOMÍA LATINOAMERICANA, 22(2), e3158. https://doi.org/10.55905/oelv22n2-061




Most read articles by the same author(s)