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• Wiersinga WJ Rhodes A Cheng AC Peacock SJ Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19). JAMA. (2020) 324:782–93. 10.1001/jama.2020.12839 32648899
• Chen C-L Lai C-C Luh D-L Chuang S-Y Yang K-C Yeh Y-P et al. Review of epidemic, containment strategies, clinical management, and economic evaluation of COVID-19 pandemic. J Formos Med Assoc. (2021) 120:S6–18. 10.1016/j.jfma.2021.05.022 34116896
• Mercer TR Salit M. Testing at scale during the COVID-19 pandemic. Nat Rev Genet. (2021) 22:415–26. 10.1038/s41576-021-00360-w 33948037
• Meller S Twele F ten Hagen NA Jendrny P Volk HA Diagnoses by dog noses? Real-time detection of SARS-CoV-2 infections by trained dogs. In: Paper Presented at: 32nd Annual Meeting of the German Society for Cytometry (DGfZ). Berlin: Charité – Universitätsmedizin Berlin (2022).
• Jendrny P Twele F Meller S Osterhaus ADME Schalke E Volk HA. Canine olfactory detection and its relevance to medical detection. BMC Infect Dis. (2021) 21:838. 10.1186/s12879-021-06523-8 34412582
• Shirasu M Touhara K. The scent of disease: volatile organic compounds of the human body related to disease and disorder. J Biochem. (2011) 150:257–66. 10.1093/jb/mvr090 21771869
• Broza YY Mochalski P Ruzsanyi V Amann A Haick H. Hybrid volatolomics and disease detection. Angew Chemie Int Ed. (2015) 54:11036–48. 10.1002/anie.201500153 26235374
• Angle TC Passler T Waggoner PL Fischer TD Rogers B Galik PK et al. Real-time detection of a virus using detection dogs. Front Vet Sci. (2016) 2:79. 10.3389/fvets.2015.00079 26779494
• Kamal F Kumar S Edwards MR Veselkov K Belluomo I Kebadze T et al. Virus-induced volatile organic compounds are detectable in exhaled breath during pulmonary infection. Am J Respir Crit Care Med. (2021) 204:1075–85. 10.1164/rccm.202103-0660OC 34319857
• Issitt T Wiggins L Veysey M Sweeney ST Brackenbury WJ Redeker K. Volatile compounds in human breath: critical review and meta-analysis. J Breath Res. (2022) 16:024001. 10.1088/1752-7163/ac5230 35120340
• Pirrone F Albertini M. Olfactory detection of cancer by trained sniffer dogs: a systematic review of the literature. J Vet Behav. (2017) 19:105–17. 10.1016/j.jveb.2017.03.004
• Hardin DS Anderson W Cattet J. Dogs can be successfully trained to alert to hypoglycemia samples from patients with type 1 diabetes. Diabetes Ther. (2015) 6:509–17. 10.1007/s13300-015-0135-x 26440208
• Catala A Grandgeorge M Schaff J-L Cousillas H Hausberger M Cattet J. Dogs demonstrate the existence of an epileptic seizure odour in humans. Sci Rep. (2019) 9:4103. 10.1038/s41598-019-40721-4 30923326
• Maa E Arnold J Ninedorf K Olsen H. Canine detection of volatile organic compounds unique to human epileptic seizure. Epilepsy Behav. (2021) 115:107690. 10.1016/j.yebeh.2020.107690 33360399
• Maurer M McCulloch M Willey AM Hirsch W Dewey D. Detection of bacteriuria by canine olfaction. Open Forum Infect Dis. (2016) 3:ofw051. 10.1093/ofid/ofw051 27186578
• Taylor MT McCready J Broukhanski G Kirpalaney S Lutz H Powis J. Using dog scent detection as a point-of-care tool to identify toxigenic Clostridium difficile in stool. Open Forum Infect Dis. (2018) 5:ofy179. 10.1093/ofid/ofy179 30151408
• Guest C Pinder M Doggett M Squires C Affara M Kandeh B et al. Trained dogs identify people with malaria parasites by their odour. Lancet Infect Dis. (2019) 19:578–80. 10.1016/S1473-3099(19)30220-8
• Kataoka H Saito K Kato H Masuda K. Noninvasive analysis of volatile biomarkers in human emanations for health and early disease diagnosis. Bioanalysis. (2013) 5:1443–59. 10.4155/bio.13.85 23742311
• Rattray NJW Hamrang Z Trivedi DK Goodacre R Fowler SJ. Taking your breath away: metabolomics breathes life in to personalized medicine. Trends Biotechnol. (2014) 32:538–48. 10.1016/j.tibtech.2014.08.003 25179940
• Cambau E Poljak M. Sniffing animals as a diagnostic tool in infectious diseases. Clin Microbiol Infect. (2020) 26:431–5. 10.1016/j.cmi.2019.10.036 31734357
• Bauër P Leemans M. Remote Medical Scent Detection of Cancer and Infectious Diseases With Dogs and Rats: A Systematic Review. Research Square [Preprint]. (2021). Available online at: https://assets.researchsquare.com/files/rs-753298/v1/3d37a663-6815-403d-ba28-60910f3f14e6.pdf?c=1644333652 (accessed August 7, 2022).
• Horvath G Järverud GA Järverud S Horváth I. Human ovarian carcinomas detected by specific odor. Integr Cancer Ther. (2008) 7:76–80. 10.1177/1534735408319058 18505901
• Ehmann R Boedeker E Friedrich U Sagert J Dippon J Friedel G et al. Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon. Eur Respir J. (2012) 39:669–76. 10.1183/09031936.00051711 21852337
• Kybert N Prokop-Prigge K Otto CM Ramirez L Joffe E Tanyi J et al. Exploring ovarian cancer screening using a combined sensor approach: a pilot study. AIP Adv. (2020) 10:035213. 10.1063/1.5144532
• Rodríguez-Aguilar M Díaz de León-Martínez L Gorocica-Rosete P Pérez-Padilla R Domínguez-Reyes CA Tenorio-Torres JA et al. Application of chemoresistive gas sensors and chemometric analysis to differentiate the fingerprints of global volatile organic compounds from diseases. Preliminary results of COPD, lung cancer and breast cancer. Clin Chim Acta. (2021) 518:83–92. 10.1016/j.cca.2021.03.016 33766555
• van de Kant KDG van der Sande LJTM Jöbsis Q van Schayck OCP Dompeling E. Clinical use of exhaled volatile organic compounds in pulmonary diseases: a systematic review. Respir Res. (2012) 13:117. 10.1186/1465-9921-13-117 23259710
• Sethi S Nanda R Chakraborty T. Clinical application of volatile organic compound analysis for detecting infectious diseases. Clin Microbiol Rev. (2013) 26:462–75. 10.1128/CMR.00020-13 23824368
• Traxler S Bischoff A-C Saß R Trefz P Gierschner P Brock B et al. VOC breath profile in spontaneously breathing awake swine during influenza A infection. Sci Rep. (2018) 8:14857. 10.1038/s41598-018-33061-2 30291257
• Aksenov AA Sandrock CE Zhao W Sankaran S Schivo M Harper R et al. Cellular scent of influenza virus infection. Chembiochem. (2014) 15:1040–8. 10.1002/cbic.201300695 24719290
• Gould O Ratcliffe N Król E de Lacy Costello B. Breath analysis for detection of viral infection, the current position of the field. J Breath Res. (2020) 14:041001. 10.1088/1752-7163/ab9c32 32531777
• Shen B Yi X Sun Y Bi X Du J Zhang C et al. Proteomic and metabolomic characterization of COVID-19 patient sera. Cell. (2020) 182:59–72. 10.1016/j.cell.2020.05.032 32492406
• Lamote K Janssens E Schillebeeckx E Lapperre TS De Winter BY van Meerbeeck JP. The scent of COVID-19: viral (semi-)volatiles as fast diagnostic biomarkers? J Breath Res. (2020) 14:042001. 10.1088/1752-7163/aba105 32599571
• Ruszkiewicz DM Sanders D O’Brien R Hempel F Reed MJ Riepe AC et al. Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry – A feasibility study. EClinicalMedicine. (2020) 2:100609. 10.1016/j.eclinm.2020.100609 33134902
• Berna AZ Akaho EH Harris RM Congdon M Korn E Neher S et al. Reproducible breath metabolite changes in children with SARS-CoV-2 infection. ACS Infect Dis. (2021) 7:2596–603. 10.1021/acsinfecdis.1c00248 34319698
• Chen H Qi X Zhang L Li X Ma J Zhang C et al. COVID-19 screening using breath-borne volatile organic compounds. J Breath Res. (2021) 15:047104. 10.1088/1752-7163/ac2e57 34624875
• Grassin-Delyle S Roquencourt C Moine P Saffroy G Carn S Heming N et al. Metabolomics of exhaled breath in critically ill COVID-19 patients: a pilot study. EBioMedicine. (2021) 63:103154. 10.1016/j.ebiom.2020.103154 33279860
• Ibrahim W Cordell RL Wilde MJ Richardson M Carr L Sundari Devi Dasi A et al. Diagnosis of COVID-19 by exhaled breath analysis using gas chromatography–mass spectrometry. ERJ Open Res. (2021) 7:00139–02021. 10.1183/23120541.00139-2021 34235208
• Marder D Tzanani N Baratz A Drug E Prihed H Weiss S et al. A multiple-method comparative study using GC–MS, AMDIS and in-house-built software for the detection and identification of “unknown” volatile organic compounds in breath. J Mass Spectrom. (2021) 56:e4782. 10.1002/jms.4782 34523187
• Feuerherd M Sippel A-K Erber J Baumbach JI Schmid RM Protzer U 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. Sci Rep. (2021) 11:20143. 10.1038/s41598-021-99742-7 34635788
• Steppert C Steppert I Sterlacci W Bollinger T. Rapid detection of SARS-CoV-2 infection by multicapillary column coupled ion mobility spectrometry (MCC-IMS) of breath. A proof of concept study. J Breath Res. (2021) 15:027105. 10.1088/1752-7163/abe5ca 33578396
• ten Hagen NA Twele F Meller S Jendrny P Schulz C von Köckritz-Blickwede M et al. Discrimination of SARS-CoV-2 infections from other viral respiratory infections by scent detection dogs. Front Med. (2021) 8:749588. 10.3389/fmed.2021.749588 34869443
• Harper WJ. The strengths and weaknesses of the electronic nose. In: Rouseff R Cadwallader K editors. Headspace Analysis of Foods and Flavors. Advances in Experimental Medicine and Biology. Boston, MA: Springer (2001). p. 59–71. 10.1007/978-1-4615-1247-9_5
• Zohora SE Khan AM Hundewale N. Chemical sensors employed in electronic noses: a review. In: Meghanathan N Nagamalai D Chaki N editors. Advances in Computing and Information Technology. Advances in Intelligent Systems and Computing. Berlin: Springer (2013). p. 177–84. 10.1007/978-3-642-31600-5_18
• Hu W Wan L Jian Y Ren C Jin K Su X et al. Electronic noses: from advanced materials to sensors aided with data processing. Adv Mater Technol. (2019) 4:1800488. 10.1002/admt.201800488
• Rodríguez-Aguilar M Díaz de León-Martínez L Zamora-Mendoza BN Comas-García A Guerra Palomares SE García-Sepúlveda CA et al. Comparative analysis of chemical breath-prints through olfactory technology for the discrimination between SARS-CoV-2 infected patients and controls. Clin Chim Acta. (2021) 519:126–32. 10.1016/j.cca.2021.04.015 33901429
• Wintjens AGWE Hintzen KFH Engelen SME Lubbers T Savelkoul PHM Wesseling G et al. Applying the electronic nose for pre-operative SARS-CoV-2 screening. Surg Endosc. (2021) 35:6671–8. 10.1007/s00464-020-08169-0 33269428
• Guest C Dewhirst SY Lindsay SW Allen DJ Aziz S Baerenbold O et al. Using trained dogs and organic semi-conducting sensors to identify asymptomatic and mild SARS-CoV-2 infections: an observational study. J Travel Med. (2022) 29:taac043. 10.1093/jtm/taac043 35325195
• Shan B Broza YY Li W Wang Y Wu S Liu Z et al. Multiplexed nanomaterial-based sensor array for detection of COVID-19 in exhaled breath. ACS Nano. (2020) 14:12125–32. 10.1021/acsnano.0c05657 32808759
• Zamora-Mendoza BN Díaz de León-Martínez L Rodríguez-Aguilar M Mizaikoff B Flores-Ramírez R. 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. (2022) 236:122832. 10.1016/j.talanta.2021.122832 34635222
• Snitz K Andelman-Gur M Pinchover L Weissgross R Weissbrod A Mishor E et al. Proof of concept for real-time detection of SARS CoV-2 infection with an electronic nose. PLoS One. (2021) 16:e0252121. 10.1371/journal.pone.0252121 34077435
• Grandjean D Salmon D Slama D Gallet C Julien C Seyrat E et al. Screening for SARS-CoV-2 persistence in long COVID patients using sniffer dogs and scents from axillary sweats samples. J Clin Trials. (2022) 12:1000002.
• Twele F ten Hagen NA Meller S Schulz C Osterhaus A Jendrny P et al. Detection of post-COVID-19 patients using medical scent detection dogs—a pilot study. Front Med. (2022) 9:877259. 10.3389/fmed.2022.877259 35783627
• Vinaixa M Schymanski EL Neumann S Navarro M Salek RM Yanes O. Mass spectral databases for LC/MS- and GC/MS-based metabolomics: state of the field and future prospects. Trends Anal Chem. (2016) 78:23–35. 10.1016/j.trac.2015.09.005
• Ligor M Ligor T Bajtarevic A Ager C Pienz M Klieber M et al. Determination of volatile organic compounds in exhaled breath of patients with lung cancer using solid phase microextraction and gas chromatography mass spectrometry. Clin Chem Lab Med. (2009) 47:550–60. 10.1515/CCLM.2009.133 19397483
• Ulanowska A Kowalkowski T Trawińska E Buszewski B. The application of statistical methods using VOCs to identify patients with lung cancer. J Breath Res. (2011) 5:046008. 10.1088/1752-7155/5/4/046008
• van Oort P de Bruin S Weda H Knobel H Schultz M Bos L. Exhaled breath metabolomics for the diagnosis of pneumonia in intubated and mechanically-ventilated intensive care unit (ICU)-patients. Int J Mol Sci. (2017) 18:449. 10.3390/ijms18020449 28218729
• Schleich FN Zanella D Stefanuto P-H Bessonov K Smolinska A Dallinga JW et al. Exhaled volatile organic compounds are able to discriminate between neutrophilic and eosinophilic asthma. Am J Respir Crit Care Med. (2019) 200:444–53. 10.1164/rccm.201811-2210OC 30973757
• James D Scott SM Ali Z O’Hare WT. Chemical sensors for electronic nose systems. Microchim Acta. (2005) 149:1–17. 10.1007/s00604-004-0291-6
• Jalal AH Alam F Roychoudhury S Umasankar Y Pala N Bhansali S. Prospects and challenges of volatile organic compound sensors in human healthcare. ACS Sens. (2018) 3:1246–63. 10.1021/acssensors.8b00400 29879839
• Phillips M Herrera J Krishnan S Zain M Greenberg J Cataneo RN. Variation in volatile organic compounds in the breath of normal humans. J Chromatogr B Biomed Sci Appl. (1999) 729:75–88. 10.1016/S0378-4347(99)00127-9
• Walker DB Walker JC Cavnar PJ Taylor JL Pickel DH Hall SB et al. Naturalistic quantification of canine olfactory sensitivity. Appl Anim Behav Sci. (2006) 97:241–54. 10.1016/j.applanim.2005.07.009
• Craven BA Paterson EG Settles GS. The fluid dynamics of canine olfaction: unique nasal airflow patterns as an explanation of macrosmia. J R Soc Interface. (2010) 7:933–43. 10.1098/rsif.2009.0490 20007171
• Concha AR Guest CM Harris R Pike TW Feugier A Zulch H et al. Canine olfactory thresholds to amyl acetate in a biomedical detection scenario. Front Vet Sci. (2019) 5:345. 10.3389/fvets.2018.00345 30723722
• Schmidt K Podmore I. Current challenges in volatile organic compounds analysis as potential biomarkers of cancer. J Biomark. (2015) 2015:981458. 10.1155/2015/981458 26317039
• Wojnowski W Kalinowska K. Machine learning and electronic noses for medical diagnostics. In: Lidströmer N Ashrafian H editors. Artificial Intelligence in Medicine. Cham: Springer International Publishing (2021). p. 1–17. 10.1007/978-3-030-58080-3_329-1
• D’Aniello B Pinelli C Varcamonti M Rendine M Lombardi P Scandurra A. COVID sniffer dogs: technical and ethical concerns. Front Vet Sci. (2021) 8:669712. 10.3389/fvets.2021.669712 34235201
• Hackner K Pleil J. Canine olfaction as an alternative to analytical instruments for disease diagnosis: understanding ‘dog personality’ to achieve reproducible results. J Breath Res. (2017) 11:012001. 10.1088/1752-7163/aa5524 28068294
• McGowan RTS Rehn T Norling Y Keeling LJ. Positive affect and learning: exploring the “Eureka Effect” in dogs. Anim Cogn. (2014) 17:577–87. 10.1007/s10071-013-0688-x 24096703
• Kantele A Paajanen J Turunen S Pakkanen SH Patjas A Itkonen L et al. Scent dogs in detection of COVID-19: triple-blinded randomised trial and operational real-life screening in airport setting. BMJ Glob Health. (2022) 7:e008024. 10.1136/bmjgh-2021-008024 35577391
• Maurer M Seto T Guest C Somal A Julian C. Detection of SARS-CoV-2 by canine olfaction: a pilot study. Open Forum Infect Dis. (2022) 9:ofac226. 10.1093/ofid/ofac226 35818366
• ten Hagen NA Twele F Meller S Wijnen L Schulz C Schoneberg C et al. Canine real-time detection of SARS-CoV-2 infections in the context of a mass screening event. BMJ Glob Health. (2022) 7:e010276. 10.1136/bmjgh-2022-010276 36368765
• Bremhorst A Bütler S Würbel H Riemer S. Incentive motivation in pet dogs – Preference for constant vs varied food rewards. Sci Rep. (2018) 8:9756. 10.1038/s41598-018-28079-5 29950698
• Gazit I Terkel J. Explosives detection by sniffer dogs following strenuous physical activity. Appl Anim Behav Sci. (2003) 81:149–61. 10.1016/S0168-1591(02)00274-5
• Slensky KA Drobatz KJ Downend AB Otto CM. Deployment morbidity among search-and-rescue dogs used after the September 11, 2001, terrorist attacks. J Am Vet Med Assoc. (2004) 225:868–73. 10.2460/javma.2004.225.868 15485045
• Wackermannová M Pinc L Jebavý L. Olfactory sensitivity in mammalian species. Physiol Res. (2016) 65:369–90. 10.33549/physiolres.932955 27070753
• Jamieson LTJ Baxter GS Murray PJ. Identifying suitable detection dogs. Appl Anim Behav Sci. (2017) 195:1–7. 10.1016/j.applanim.2017.06.010
• Kokocińska-Kusiak A Woszczyło M Zybala M Maciocha J Barłowska K Dziêcioł M. Canine olfaction: physiology, behavior, and possibilities for practical applications. Animals. (2021) 11:2463. 10.3390/ani11082463 34438920
• Fleischer J Breer H Strotmann J. Mammalian olfactory receptors. Front Cell Neurosci. (2009) 3:9. 10.3389/neuro.03.009.2009 19753143
• Issel-Tarver L Rine J. Organization and expression of canine olfactory receptor genes. Proc Natl Acad Sci U.S.A. (1996) 93:10897–902. 10.1073/pnas.93.20.10897 8855279
• Tacher S Quignon P Rimbault M Dreano S Andre C Galibert F. Olfactory receptor sequence polymorphism within and between breeds of dogs. J Hered. (2005) 96:812–6. 10.1093/jhered/esi113 16251519
• Lesniak A Walczak M Jezierski T Sacharczuk M Gawkowski M Jaszczak K. Canine olfactory receptor gene polymorphism and its relation to odor detection performance by sniffer dogs. J Hered. (2008) 99:518–27. 10.1093/jhered/esn057 18664716
• Robin S Tacher S Rimbault M Vaysse A Dréano S André C et al. Genetic diversity of canine olfactory receptors. BMC Genomics. (2009) 10:21. 10.1186/1471-2164-10-21 19144169
• Chen R Irwin DM Zhang Y-P. Differences in selection drive olfactory receptor genes in different directions in dogs and wolf. Mol Biol Evol. (2012) 29:3475–84. 10.1093/molbev/mss153 22683813
• Rauth-Widmann B. Your Dog’s Senses: Understand how he Perceives his World. München: Cadmos (2006). p. 111.
• Polgár Z Kinnunen M Újváry D Miklósi Á Gácsi M. A test of canine olfactory capacity: comparing various dog breeds and wolves in a natural detection task. PLoS One. (2016) 11:e0154087. 10.1371/journal.pone.0154087 27152412
• Packer R Hendricks A Burn C. Do dog owners perceive the clinical signs related to conformational inherited disorders as “normal” for the breed? A potential constraint to improving canine welfare. Anim Welf. (2012) 21:81–93. 10.7120/096272812X13345905673809
• Bartels A Martin V Bidoli E Steigmeier-Raith S Brühschwein A Reese S et al. Brachycephalic problems of pugs relevant to animal welfare. Anim Welf. (2015) 24:327–33. 10.7120/09627286.24.3.327
• Oechtering TH Oechtering GU Noeller C. Computed tomographic imaging of the nose in brachycephalic dog breeds. Tierärztl Prax. (2007) 35:177–87.
• Hall NJ Glenn K Smith DW Wynne CDL. Performance of pugs, german shepherds, and greyhounds (Canis lupus familiaris) on an odor-discrimination task. J Comp Psychol. (2015) 129:237–46. 10.1037/a0039271 26010195
• Craven BA Neuberger T Paterson EG Webb AG Josephson EM Morrison EE et al. Reconstruction and morphometric analysis of the nasal airway of the dog (Canis familiaris) and implications regarding olfactory airflow. Anat Rec. (2007) 290:1325–40. 10.1002/ar.20592 17929289
• Negus VE. The Comparative Anatomy and Physiology of the Nose and Paranasal Sinuses. Edinburgh: Livingstone (1958). p. 402.
• Wagner F Ruf I. Who nose the borzoi? Turbinal skeleton in a dolichocephalic dog breed (Canis lupus familiaris). Mamm Biol. (2019) 94:106–19. 10.1016/j.mambio.2018.06.005
• Beebe SC Howell TJ Bennett PC. Using scent detection dogs in conservation settings: a review of scientific literature regarding their selection. Front Vet Sci. (2016) 3:96. 10.3389/fvets.2016.00096 27840815
• Cablk ME Heaton JS. Accuracy and reliability of dogs in surveying for desert tortoise (Gopherus agassizii). Ecol Appl. (2006) 16:1926–35. 10.1890/1051-0761(2006)016[1926:aarodi]2.0.co;2 17069383
• Hurt A Smith DA. Conservation dogs. In: Helton WS editor. Canine Ergonomics: The Science of Working Dogs. Boca Raton, FL: CRC Press (2009). p. 175–94.
• McGarrity ME Sinn DL Thomas SG Marti CN Gosling SD. Comparing the predictive validity of behavioral codings and behavioral ratings in a working-dog breeding program. Appl Anim Behav Sci. (2016) 179:82–94. 10.1016/j.applanim.2016.03.013
• Wilsson E Sundgren P-E. The use of a behaviour test for the selection of dogs for service and breeding, I: method of testing and evaluating test results in the adult dog, demands on different kinds of service dogs, sex and breed differences. Appl Anim Behav Sci. (1997) 53:279–95. 10.1016/S0168-1591(96)01174-4
• Rebmann A David E Sorg MHH. Cadaver Dog Handbook: Forensic Training and Tactics for the Recovery of Human Remains. Boca Raton, FL: CRC Press (2000).
• Rooney NJ Bradshaw JWS. Breed and sex differences in the behavioural attributes of specialist search dogs—a questionnaire survey of trainers and handlers. Appl Anim Behav Sci. (2004) 86:123–35. 10.1016/j.applanim.2003.12.007
• Wei Q Zhang H Ma S Guo D. Sex- and age-related differences in c-fos expression in dog olfactory bulbs. Acta Zool. (2017) 98:370–6. 10.1111/azo.12178
• Hart BL Eckstein RA. The role of gonadal hormones in the occurrence of objectionable behaviours in dogs and cats. Appl Anim Behav Sci. (1997) 52:331–44. 10.1016/S0168-1591(96)01133-1
• Maejima M Inoue-Murayama M Tonosaki K Matsuura N Kato S Saito Y et al. Traits and genotypes may predict the successful training of drug detection dogs. Appl Anim Behav Sci. (2007) 107:287–98. 10.1016/j.applanim.2006.10.005
• Wells DL Hepper PG. Directional tracking in the domestic dog, Canis familiaris. Appl Anim Behav Sci. (2003) 84:297–305. 10.1016/j.applanim.2003.08.009
• Myers LJ Nusbaum KE Swango LJ Hanrahan LN Sartin E. Dysfunction of sense of smell caused by canine parainfluenza virus infection in dogs. Am J Vet Res. (1988) 49:188–90. 2831762
• Myers LJ. Dysosmia of the dog in clinical veterinary medicine. Prog Vet Neurol. (1990) 1:171–9.
• Butowt R Bilinska K. SARS-CoV-2: olfaction, brain infection, and the urgent need for clinical samples allowing earlier virus detection. ACS Chem Neurosci. (2020) 11:1200–3. 10.1021/acschemneuro.0c00172 32283006
• Bryche B St Albin A Murri S Lacôte S Pulido C Ar Gouilh M et al. Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters. Brain Behav Immun. (2020) 89:579–86. 10.1016/j.bbi.2020.06.032 32629042
• Ye Q Zhou J He Q Li R-T Yang G Zhang Y et al. SARS-CoV-2 infection in the mouse olfactory system. Cell Discov. (2021) 7:49. 10.1038/s41421-021-00290-1 34230457
• Calvet GA Pereira SA Ogrzewalska M Pauvolid-Corrêa A Resende PC de Tassinari WS et al. Investigation of SARS-CoV-2 infection in dogs and cats of humans diagnosed with COVID-19 in Rio de Janeiro, Brazil. PLoS One. (2021) 16:e0250853. 10.1371/journal.pone.0250853 33909706
• Hamer SA Pauvolid-Corrêa A Zecca IB Davila E Auckland LD Roundy CM et al. SARS-CoV-2 infections and viral isolations among serially tested cats and dogs in households with infected owners in Texas, USA. Viruses. (2021) 13:938. 10.3390/v13050938 34069453
• Shi J Wen Z Zhong G Yang H Wang C Huang B et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2. Science. (2020) 368:1016–20. 10.1126/science.abb7015 32269068
• Hirai T Kojima S Shimada A Umemura T Sakai M Itakurat C. Age-related changes in the olfactory system of dogs. Neuropathol Appl Neurobiol. (1996) 22:531–9. 10.1111/j.1365-2990.1996.tb01132.x 9004244
• Salvin HE McGreevy PD Sachdev PS Valenzuela MJ. The canine cognitive dysfunction rating scale (CCDR): a data-driven and ecologically relevant assessment tool. Vet J. (2011) 188:331–6. 10.1016/j.tvjl.2010.05.014 20542455
• Schütt T Toft N Berendt M. Cognitive function, progression of age-related behavioral changes, biomarkers, and survival in dogs more than 8 years old. J Vet Intern Med. (2015) 29:1569–77. 10.1111/jvim.13633 26463980
• Ozawa M Inoue M Uchida K Chambers JK Takeuch Y Nakayama H. Physical signs of canine cognitive dysfunction. J Vet Med Sci. (2019) 81:1829–34. 10.1292/jvms.19-0458 31685716
• Kjelvik G Saltvedt I White LR Stenumgård P Sletvold O Engedal K et al. The brain structural and cognitive basis of odor identification deficits in mild cognitive impairment and Alzheimer’s disease. BMC Neurol. (2014) 14:168. 10.1186/s12883-014-0168-1 25154749
• Chaber A Hazel S Matthews B Withers A Alvergnat G Grandjean D et al. Evaluation of canine detection of COVID-19 infected individuals under controlled settings. Transbound Emerg Dis. (2022) 69:e1951–8. 10.1111/tbed.14529 35316576
• Vesga O Agudelo M Valencia-Jaramillo AF Mira-Montoya A Ossa-Ospina F Ocampo E et al. Highly sensitive scent-detection of COVID-19 patients in vitro by trained dogs. PLoS One. (2021) 16:e0257474. 10.1371/journal.pone.0257474 34587181
• Horowitz A Hecht J Dedrick A. Smelling more or less: investigating the olfactory experience of the domestic dog. Learn Motiv. (2013) 44:207–17. 10.1016/j.lmot.2013.02.002
• Jenkins EK DeChant MT Perry EB. When the nose doesn’t know: canine olfactory function associated with health, management, and potential links to microbiota. Front Vet Sci. (2018) 5:56. 10.3389/fvets.2018.00056 29651421
• Bräuer J Blasi D. Dogs display owner-specific expectations based on olfaction. Sci Rep. (2021) 11:3291. 10.1038/s41598-021-82952-4 33558638
• Otto CM Hare E Nord JL Palermo SM Kelsey KM Darling TA et al. Evaluation of three hydration strategies in detection dogs working in a hot environment. Front Vet Sci. (2017) 4:174. 10.3389/fvets.2017.00174 29124059
• Jezierski T Adamkiewicz E Walczak M Sobczyńska M Górecka-Bruzda A Ensminger J et al. Efficacy of drug detection by fully-trained police dogs varies by breed, training level, type of drug and search environment. Forensic Sci Int. (2014) 237:112–8. 10.1016/j.forsciint.2014.01.013 24631776
• Lazarowski L Haney PS Brock J Fischer T Rogers B Angle C et al. Investigation of the behavioral characteristics of dogs purpose-bred and prepared to perform vapor wake® detection of person-borne explosives. Front Vet Sci. (2018) 5:50. 10.3389/fvets.2018.00050 29616229
• Angle CT Wakshlag JJ Gillette RL Steury T Haney P Barrett J et al. The effects of exercise and diet on olfactory capability in detection dogs. J Nutr Sci. (2014) 3:e44. 10.1017/jns.2014.35 26106477
• Altom EK Davenport GM Myers LJ Cummins KA. Effect of dietary fat source and exercise on odorant-detecting ability of canine athletes. Res Vet Sci. (2003) 75:149–55. 10.1016/S0034-5288(03)00071-7
• Jenkins EK Lee-Fowler TM Angle TC Behrend EN Moore GE. Effects of oral administration of metronidazole and doxycycline on olfactory capabilities of explosives detection dogs. Am J Vet Res. (2016) 77:906–12. 10.2460/ajvr.77.8.906 27463556
• Ezeh PI Myers LJ Hanrahan LA Kemppainen RJ Cummins KA. Effects of steroids on the olfactory function of the dog. Physiol Behav. (1992) 51:1183–7. 10.1016/0031-9384(92)90306-M
• Moser AY Bizo L Brown WY. Olfactory generalization in detector dogs. Animals. (2019) 9:702. 10.3390/ani9090702 31546835
• Reeve C Koivusalo M. Biomedical scent detection dogs: would they pass as a health technology? Pet Behav Sci. (2018) 6:1–7. 10.21071/pbs.v0i6.10785
• Waggoner P Lazarowski L Hutchings B Angle C Porritt F. Effects of learning an increasing number of odors on olfactory learning, memory and generalization in detection dogs. Appl Anim Behav Sci. (2022) 247:105568. 10.1016/j.applanim.2022.105568
• Lit L Schweitzer JB Oberbauer AM. Handler beliefs affect scent detection dog outcomes. Anim Cogn. (2011) 14:387–94. 10.1007/s10071-010-0373-2 21225441
• Jendrny P Schulz C Twele F Meller S Von Köckritz-Blickwede M Osterhaus ADME et al. Scent dog identification of samples from COVID-19 patients – A pilot study. BMC Infect Dis. (2020) 20:536. 10.1186/s12879-020-05281-3 32703188
• Jendrny P Twele F Meller S Schulz C Von Köckritz-Blickwede M Osterhaus ADME et al. Scent dog identification of SARS-CoV-2 infections in different body fluids. BMC Infect Dis. (2021) 21:707. 10.1186/s12879-021-06411-1 34315418
• Aviles-Rosa EO Gallegos SF Prada-Tiedemann PA Hall NJ. An automated canine line-up for detection dog research. Front Vet Sci. (2021) 8:775381. 10.3389/fvets.2021.775381 35071382
• Bosco-Lauth AM Hartwig AE Porter SM Gordy PW Nehring M Byas AD et al. Experimental infection of domestic dogs and cats with SARS-CoV-2: pathogenesis, transmission, and response to reexposure in cats. Proc Natl Acad Sci U.S.A. (2020) 117:26382–8. 10.1073/pnas.2013102117 32994343
• Patterson EI Elia G Grassi A Giordano A Desario C Medardo M et al. Evidence of exposure to SARS-CoV-2 in cats and dogs from households in Italy. Nat Commun. (2020) 11:6231. 10.1038/s41467-020-20097-0 33277505
• Sit THC Brackman CJ Ip SM Tam KWS Law PYT To EMW et al. Infection of dogs with SARS-CoV-2. Nature. (2020) 586:776–8. 10.1038/s41586-020-2334-5 32408337
• Decaro N Vaccari G Lorusso A Lorusso E De Sabato L Patterson EI et al. Possible human-to-dog transmission of SARS-CoV-2. Italy, 2020. Emerg Infect Dis. (2021) 27:1981–4. 10.3201/eid2707.204959 33979566
• Barroso R Vieira-Pires A Antunes A Fidalgo-Carvalho I. Susceptibility of pets to SARS-CoV-2 infection: lessons from a seroepidemiologic survey of cats and dogs in Portugal. Microorganisms. (2022) 10:345. 10.3390/microorganisms10020345 35208799
• Ferasin L Fritz M Ferasin H Becquart P Corbet S Ar Gouilh M et al. Infection with SARS-CoV-2 variant B.1.1.7 detected in a group of dogs and cats with suspected myocarditis. Vet Rec. (2021) 189:e944. 10.1002/vetr.944 34738231
• Schulz C Martina B Mirolo M Müller E Klein R Volk H et al. SARS-CoV-2–specific antibodies in domestic cats during first COVID-19 wave, Europe. Emerg Infect Dis. (2021) 27:3115–8. 10.3201/eid2712.211252 34695368
• Schulz C Wylezich C Wernike K Gründl M Dangel A Baechlein C et al. Prolonged SARS-CoV-2 RNA shedding from therapy cat after cluster outbreak in retirement home. Emerg Infect Dis. (2021) 27:1974–6. 10.3201/eid2707.204670 34152973
• Eskandari E Ahmadi Marzaleh M Roudgari H Hamidi Farahani R Nezami-Asl A Laripour R et al. Sniffer dogs as a screening/diagnostic tool for COVID-19: a proof of concept study. BMC Infect Dis. (2021) 21:243. 10.1186/s12879-021-05939-6 33673823
• Essler JL Kane SA Nolan P Akaho EH Berna AZ DeAngelo A et al. Discrimination of SARS-CoV-2 infected patient samples by detection dogs: a proof of concept study. PLoS One. (2021) 16:e0250158. 10.1371/journal.pone.0250158 33852639
• Mendel J Frank K Edlin L Hall K Webb D Mills J et al. Preliminary accuracy of COVID-19 odor detection by canines and HS-SPME-GC-MS using exhaled breath samples. Forensic Sci Int Synerg. (2021) 3:100155. 10.1016/j.fsisyn.2021.100155 34127961
• Salgirli Y Kismali G Saral B Sareyyüpoğlu B Habiloğlu AD Öztürk H et al. Development of a Safety Protocol for Training and Using SARS-CoV-2 Detection Dogs. J Vet Behav [Preprint]. (2022). Available online at: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4075240# (accessed July 6, 2022).
• Hong KH Lee SW Kim TS Huh HJ Lee J Kim SY et al. Guidelines for laboratory diagnosis of coronavirus disease 2019 (COVID-19) in Korea. Ann Lab Med. (2020) 40:351–60. 10.3343/alm.2020.40.5.351 32237288
• Hsieh W-Y Lin C-H Lin T-C Lin C-H Chang H-F Tsai C-H et al. Development and efficacy of lateral flow point-of-care testing devices for rapid and mass COVID-19 diagnosis by the detections of SARS-CoV-2 antigen and anti-SARS-CoV-2 antibodies. Diagnostics. (2021) 11:1760. 10.3390/diagnostics11101760 34679458
• Mohammadi A Esmaeilzadeh E Li Y Bosch RJ Li JZ. SARS-CoV-2 detection in different respiratory sites: a systematic review and meta-analysis. EBioMedicine. (2020) 59:102903. 10.1016/j.ebiom.2020.102903 32718896
• Yoon JG Yoon J Song JY Yoon S-Y Lim CS Seong H et al. Clinical significance of a high SARS-CoV-2 viral load in the saliva. J Korean Med Sci. (2020) 35:e195. 10.3346/jkms.2020.35.e195 32449329
• Medeiros da Silva RC Nogueira Marinho LC de Araújo Silva DN Costa de Lima K Pirih FQ Luz de Aquino Martins AR. Saliva as a possible tool for the SARS-CoV-2 detection: a review. Travel Med Infect Dis. (2020) 38:101920. 10.1016/j.tmaid.2020.101920 33220456
• Jeong HW Kim S-M Kim H-S Kim Y-I Kim JH Cho JY et al. Viable SARS-CoV-2 in various specimens from COVID-19 patients. Clin Microbiol Infect. (2020) 26:1520–4. 10.1016/j.cmi.2020.07.020 32711057
• Huang N Pérez P Kato T Mikami Y Okuda K Gilmore RC et al. SARS-CoV-2 infection of the oral cavity and saliva. Nat Med. (2021) 27:892–903. 10.1038/s41591-021-01296-8 33767405
• Liu L Wei Q Alvarez X Wang H Du Y Zhu H et al. Epithelial cells lining salivary gland ducts are early target cells of severe acute respiratory syndrome coronavirus infection in the upper respiratory tracts of rhesus macaques. J Virol. (2011) 85:4025–30. 10.1128/JVI.02292-10 21289121
• Chen L Zhao J Peng J Li X Deng X Geng Z et al. Detection of SARS-CoV-2 in saliva and characterization of oral symptoms in COVID-19 patients. Cell Prolif. (2020) 53:e12923. 10.1111/cpr.12923 33073910
• Xu R Cui B Duan X Zhang P Zhou X Yuan Q. Saliva: potential diagnostic value and transmission of 2019-nCoV. Int J Oral Sci. (2020) 12:11. 10.1038/s41368-020-0080-z 32300101
• Han MS Seong M-W Kim N Shin S Cho SI Park H et al. Viral RNA load in mildly symptomatic and asymptomatic children with COVID-19, Seoul, South Korea. Emerg Infect Dis. (2020) 26:2497–9. 10.3201/eid2610.202449 32497001
• Iwasaki S Fujisawa S Nakakubo S Kamada K Yamashita Y Fukumoto T et al. Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva. J Infect. (2020) 81:e145–7. 10.1016/j.jinf.2020.05.071 32504740
• Kim SE Lee JY Lee A Kim S Park K-H Jung S-I et al. Viral load kinetics of SARS-CoV-2 infection in saliva in Korean patients: a prospective multi-center comparative study. J Korean Med Sci. (2020) 35:e287. 10.3346/jkms.2020.35.e287 32776725
• Procop GW Shrestha NK Vogel S Van Sickle K Harrington S Rhoads DD et al. A direct comparison of enhanced saliva to nasopharyngeal swab for the detection of SARS-CoV-2 in symptomatic patients. J Clin Microbiol. (2020) 58:e01946–20. 10.1128/JCM.01946-20 32883744
• To KK Tsang OT-Y Leung W Tam AR Wu T Lung DC et al. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. (2020) 20:565–74. 10.1016/S1473-3099(20)30196-1
• Williams E Bond K Zhang B Putland M Williamson DA. Saliva as a noninvasive specimen for detection of SARS-CoV-2. J Clin Microbiol. (2020) 58:e00776–20. 10.1128/JCM.00776-20 32317257
• Savela ES Viloria Winnett A Romano AE Porter MK Shelby N Akana R et al. Quantitative SARS-CoV-2 viral-load curves in paired saliva samples and nasal swabs inform appropriate respiratory sampling site and analytical test sensitivity required for earliest viral detection. J Clin Microbiol. (2022) 60:e0178521. 10.1128/JCM.01785-21 34911366
• Wyllie AL Fournier J Casanovas-Massana A Campbell M Tokuyama M Vijayakumar P et al. Saliva or nasopharyngeal swab specimens for detection of SARS-CoV-2. N Engl J Med. (2020) 383:1283–6. 10.1056/NEJMc2016359 32857487
• Kojima N Turner F Slepnev V Bacelar A Deming L Kodeboyina S et al. Self-collected oral fluid and nasal swabs demonstrate comparable sensitivity to clinician collected nasopharyngeal swabs for coronavirus disease 2019 detection. Clin Infect Dis. (2021) 73:e3106–9. 10.1093/cid/ciaa1589 33075138
• Pasomsub E Watcharananan SP Boonyawat K Janchompoo P Wongtabtim G Suksuwan W et al. Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019: a cross-sectional study. Clin Microbiol Infect. (2021) 27:285.e1–4. 10.1016/j.cmi.2020.05.001 32422408
• Zhu J Guo J Xu Y Chen X. Viral dynamics of SARS-CoV-2 in saliva from infected patients. J Infect. (2020) 81:e48–50. 10.1016/j.jinf.2020.06.059 32593658
• Penn DJ Oberzaucher E Grammer K Fischer G Soini HA Wiesler D et al. Individual and gender fingerprints in human body odour. J R Soc Interface. (2007) 4:331–40. 10.1098/rsif.2006.0182 17251141
• Soini HA Klouckova I Wiesler D Oberzaucher E Grammer K Dixon SJ et al. Analysis of volatile organic compounds in human saliva by a static sorptive extraction method and gas chromatography-mass spectrometry. J Chem Ecol. (2010) 36:1035–42. 10.1007/s10886-010-9846-7 20809147
• Wong DTW. Salivaomics. J Am Dent Assoc. (2012) 143:19S–24S. 10.14219/jada.archive.2012.0339 23034834
• Propper RE. Is sweat a possible route of transmission of SARS-CoV-2? Exp Biol Med. (2020) 245:997–8. 10.1177/1535370220935409 32551877
• Hamming I Timens W Bulthuis M Lely A Navis G van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. (2004) 203:631–7. 10.1002/path.1570 15141377
• Saponaro F Rutigliano G Sestito S Bandini L Storti B Bizzarri R et al. ACE2 in the era of SARS-CoV-2: controversies and novel perspectives. Front Mol Biosci. (2020) 7:588618. 10.3389/fmolb.2020.588618 33195436
• Liu J Li Y Liu L Hu X Wang X Hu H et al. Infection of human sweat glands by SARS-CoV-2. Cell Discov. (2020) 6:84. 10.1038/s41421-020-00229-y 33298845
• Santonja C Heras F Núñez L Requena L. COVID-19 chilblain-like lesion: immunohistochemical demonstration of SARS-CoV-2 spike protein in blood vessel endothelium and sweat gland epithelium in a polymerase chain reaction-negative patient. Br J Dermatol. (2020) 183:778–80. 10.1111/bjd.19338 32585767
• Bian X-W Yao X-H Ping Y-F Yu S Shi Y Luo T et al. Autopsy of COVID-19 patients in China. Natl Sci Rev. (2020) 7:1414–8. 10.1093/nsr/nwaa123 34192086
• Jamiolkowski D Mühleisen B Müller S Navarini AA Tzankov A Roider E. SARS-CoV-2 PCR testing of skin for COVID-19 diagnostics: a case report. Lancet. (2020) 396:598–9. 10.1016/S0140-6736(20)31754-2
• Recalcati S Tonolo S Meroni E Fantini F. SARS-CoV-2 in the sweat of COVID-19-positive patients: a possible route of transmission? J Eur Acad Dermatology Venereol. (2021) 35:e865–6. 10.1111/jdv.17607 34416062
• Arslan B Bercin S Aydogan S Islamoglu Y Dinc B. SARS-CoV-2 is not found in the sweat of COVID-19 positive patients. Irish J Med Sci. (2022) 191:27–9. 10.1007/s11845-021-02537-y 33580478
• Fathizadeh H Taghizadeh S Safari R Khiabani SS Babak B Hamzavi F et al. Study presence of COVID-19 (SARS-CoV-2) in the sweat of patients infected with COVID-19. Microb Pathog. (2020) 149:104556. 10.1016/j.micpath.2020.104556 33031898
• Munk S Münch P Stahnke L Adler-Nissen J Schieberle P. Primary odorants of laundry soiled with sweat/sebum: influence of lipase on the odor profile. J Surfactants Deterg. (2000) 3:505–15. 10.1007/s11743-000-0150-z
• Jadoon S Karim S Akram MR Kalsoom Khan A Zia MA Siddiqi AR et al. Recent developments in sweat analysis and its applications. Int J Anal Chem. (2015) 2015:164974. 10.1155/2015/164974 25838824
• Mancilla-Tapia JM Lozano-Esparza V Orduña A Osuna-Chávez RF Robles-Zepeda RE Maldonado-Cabrera B et al. Dogs detecting COVID-19 from sweat and saliva of positive people: a field experience in Mexico. Front Med. (2022) 9:837053. 10.3389/fmed.2022.837053 35433718
• Grandjean D Sarkis R Lecoq-Julien C Benard A Roger V Levesque E et al. Can the detection dog alert on COVID-19 positive persons by sniffing axillary sweat samples? A proof-of-concept study. PLoS One. (2020) 15:e0243122. 10.1371/journal.pone.0243122 33301539
• Angeletti S Travaglino F Spoto S Pascarella MC Mansi G De Cesaris M et al. COVID-19 sniffer dog experimental training: which protocol and which implications for reliable sidentification? J Med Virol. (2021) 93:5924–30. 10.1002/jmv.27147 34152634
• Grandjean D Al Marzooqi DH Lecoq-Julien C Muzzin Q Al Hammadi HK Alvergnat G et al. Use of canine olfactory detection for COVID-19 testing study on U.A.E. trained detection dog sensitivity. Open Access J Vet Sci Res. (2021) 6:000210. 10.23880/oajvsr-16000210
• de Maia RCC Alves LC da Silva JES Czyba FR Pereira JA Soistier V et al. Canine olfactory detection of SARS-COV2-infected patients: a one health approach. Front Public Health. (2021) 9:647903. 10.3389/fpubh.2021.647903 34746070
• Vlachová L Hotový G Šlechta J Váňa R Vokřálová M Zeman J. Olfactory detection of human odorant signatures in COVID patients by trained dogs. medRxiv [Preprint]. (2021). 10.1101/2021.07.12.21258827
• Devillier P Gallet C Salvator H Lecoq-Julien C Naline E Roisse D et al. Biomedical detection dogs for the identification of SARS-CoV-2 infections from axillary sweat and breath samples. J Breath Res. (2022) 16:037101. 10.1088/1752-7163/ac5d8c 35287115
• Grandjean D Elie C Gallet C Julien C Roger V Desquilbet L et al. Diagnostic accuracy of non-invasive detection of SARS-CoV-2 infection by canine olfaction. PLoS One. (2022) 17:e0268382. 10.1371/journal.pone.0268382 35648737
• Grandjean D Gallet C Julien C Sarkis R Muzzin Q Roger V et al. Identifying SARS-COV-2 infected patients through canine olfactive detection on axillary sweat samples; study of observed sensitivities and specificities within a group of trained dogs. PLoS One. (2022) 17:e0262631. 10.1371/journal.pone.0262631 35157716
• Gokool VA Crespo-Cajigas J Mallikarjun A Collins A Kane S Plymouth V et al. The use of biological sensors and instrumental analysis to discriminate COVID-19 odor signatures. Biosensors. (2022) 12:1003. 10.3390/bios12111003 36421122
• Hag-Ali M AlShamsi AS Boeijen L Mahmmod Y Manzoor R Rutten H et al. The detection dogs test is more sensitive than real-time PCR in screening for SARS-CoV-2. Commun Biol. (2021) 4:686. 10.1038/s42003-021-02232-9 34083749
• Kim JY Ko J-H Kim Y Kim Y-J Kim J-M Chung Y-S et al. Viral load kinetics of SARS-CoV-2 infection in first two patients in Korea. J Korean Med Sci. (2020) 35:e86. 10.3346/jkms.2020.35.e86 32080991
• Sun J Zhu A Li H Zheng K Zhuang Z Chen Z et al. Isolation of infectious SARS-CoV-2 from urine of a COVID-19 patient. Emerg Microbes Infect. (2020) 9:991–3. 10.1080/22221751.2020.1760144 32342724
• Peng L Liu J Xu W Luo Q Chen D Lei Z et al. SARS-CoV-2 can be detected in urine, blood, anal swabs, and oropharyngeal swabs specimens. J Med Virol. (2020) 92:1676–80. 10.1002/jmv.25936 32330305
• Lo IL Lio CF Cheong HH Lei CI Cheong TH Zhong X et al. Evaluation of SARS-CoV-2 RNA shedding in clinical specimens and clinical characteristics of 10 patients with COVID-19 in Macau. Int J Biol Sci. (2020) 16:1698–707. 10.7150/ijbs.45357 32226287
• Bwire GM Majigo MV Njiro BJ Mawazo A. Detection profile of SARS-CoV-2 using RT-PCR in different types of clinical specimens: a systematic review and meta-analysis. J Med Virol. (2021) 93:719–25. 10.1002/jmv.26349 32706393
• Jones DL Baluja MQ Graham DW Corbishley A McDonald JE Malham SK et al. Shedding of SARS-CoV-2 in feces and urine and its potential role in person-to-person transmission and the environment-based spread of COVID-19. Sci Total Environ. (2020) 749:141364. 10.1016/j.scitotenv.2020.141364 32836117
• Kashi AH De la Rosette J Amini E Abdi H Fallah-Karkan M Vaezjalali M. Urinary viral shedding of COVID-19 and its clinical associations: a systematic review and meta-analysis of observational studies. Urol J. (2020) 17:433–41. 10.22037/uj.v16i7.6248 32888186
• Nomoto H Ishikane M Katagiri D Kinoshita N Nagashima M Sadamasu K et al. Cautious handling of urine from moderate to severe COVID-19 patients. Am J Infect Control. (2020) 48:969–71. 10.1016/j.ajic.2020.05.034 32502614
• Roshandel MR Nateqi M Lak R Aavani P Sari Motlagh R Shariat SF et al. Diagnostic and methodological evaluation of studies on the urinary shedding of SARS-CoV-2, compared to stool and serum: a systematic review and meta-analysis. Cell Mol Biol. (2020) 66:148–56. 10.14715/cmb/2020.66.6.26
• Joukar F Yaghubi Kalurazi T Khoshsorour M Taramian S Mahfoozi L Balou HA et al. Persistence of SARS-CoV-2 RNA in the nasopharyngeal, blood, urine, and stool samples of patients with COVID-19: a hospital-based longitudinal study. Virol J. (2021) 18:134. 10.1186/s12985-021-01599-9 34210325
• Ren X Wang S Chen X Wei X Li G Ren S et al. Multiple expression assessments of ACE2 and TMPRSS2 SARS-CoV-2 entry molecules in the urinary tract and their associations with clinical manifestations of COVID-19. Infect Drug Resist. (2020) 13:3977–90. 10.2147/IDR.S270543 33177848
• Martinez-Rojas MA Vega-Vega O Bobadilla NA. Is the kidney a target of SARS-CoV-2? Am J Physiol Physiol. (2020) 318:F1454–62. 10.1152/ajprenal.00160.2020 32412303
• George S Pal AC Gagnon J Timalsina S Singh P Vydyam P et al. Evidence for SARS-CoV-2 spike protein in the urine of COVID-19 patients. Kidney. (2021) 2:924–36. 10.34067/KID.0002172021 35373072
• Amann A Costello BDL Miekisch W Schubert J Buszewski B Pleil J et al. The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva. J Breath Res. (2014) 8:034001. 10.1088/1752-7155/8/3/034001
• Banday KM Pasikanti KK Chan ECY Singla R Rao KVS Chauhan VS et al. Use of urine volatile organic compounds to discriminate tuberculosis patients from healthy subjects. Anal Chem. (2011) 83:5526–34. 10.1021/ac200265g 21619052
• Lim SH Martino R Anikst V Xu Z Mix S Benjamin R et al. Rapid diagnosis of tuberculosis from analysis of urine volatile organic compounds. ACS Sens. (2016) 1:852–6. 10.1021/acssensors.6b00309 29057329
• Janfaza S Khorsand B Nikkhah M Zahiri J. Digging deeper into volatile organic compounds associated with cancer. Biol Methods Protoc. (2019) 4:bz014. 10.1093/biomethods/bpz014 32161807
• Duguid JP. The size and the duration of air-carriage of respiratory droplets and droplet-nuclei. Epidemiol Infect. (1946) 44:471–9. 10.1017/S0022172400019288 20475760
• Fairchild CI Stampfer JF. Particle concentration in exhaled breath. Am Ind Hyg Assoc J. (1987) 48:948–9. 10.1080/15298668791385868 3425555
• Papineni RS Rosenthal FS. The size distribution of droplets in the exhaled breath of healthy human subjects. J Aerosol Med. (1997) 10:105–16. 10.1089/jam.1997.10.105 10168531
• Miekisch W Schubert JK Noeldge-Schomburg GFE. Diagnostic potential of breath analysis—focus on volatile organic compounds. Clin Chim Acta. (2004) 347:25–39. 10.1016/j.cccn.2004.04.023 15313139
• Bourouiba L Dehandschoewercker E Bush JWM. Violent expiratory events: on coughing and sneezing. J Fluid Mech. (2014) 745:537–63. 10.1017/jfm.2014.88
• Asadi S Bouvier N Wexler AS Ristenpart WD. The coronavirus pandemic and aerosols: does COVID-19 transmit via expiratory particles? Aerosol Sci Technol. (2020) 54:635–8. 10.1080/02786826.2020.1749229 32308568
• Scheuch G. Breathing is enough: for the spread of influenza virus and SARS-CoV-2 by breathing only. J Aerosol Med Pulm Drug Deliv. (2020) 33:230–4. 10.1089/jamp.2020.1616 32552296
• Ghosh C Singh V Grandy J Pawliszyn J. Recent advances in breath analysis to track human health by new enrichment technologies. J Sep Sci. (2020) 43:226–40. 10.1002/jssc.201900769 31826324
• Lomonaco T Salvo P Ghimenti S Biagini D Vivaldi F Bonini A et al. Stability of volatile organic compounds in sorbent tubes following SARS-CoV-2 inactivation procedures. J Breath Res. (2021) 15:037102. 10.1088/1752-7163/abf0b4 33752195
• Kang S Paul Thomas CL. How long may a breath sample be stored for at –80 °C? A study of the stability of volatile organic compounds trapped onto a mixed Tenax: carbograph trap adsorbent bed from exhaled breath. J Breath Res. (2016) 10:026011. 10.1088/1752-7155/10/2/026011
• Harshman SW Mani N Geier BA Kwak J Shepard P Fan M et al. Storage stability of exhaled breath on Tenax TA. J Breath Res. (2016) 10:046008. 10.1088/1752-7155/10/4/046008
• Oakley-Girvan I Davis SW. Breath based volatile organic compounds in the detection of breast, lung, and colorectal cancers: a systematic review. Cancer Biomark. (2017) 21:29–39. 10.3233/CBM-170177 29060925
• Salman D Ibrahim W Kanabar A Joyce A Zhao B Singapuri A et al. The variability of volatile organic compounds in the indoor air of clinical environments. J Breath Res. (2022) 16:016005. 10.1088/1752-7163/ac3565 34724656
• Amal H Leja M Broza YY Tisch U Funka K Liepniece-Karele I et al. Geographical variation in the exhaled volatile organic compounds. J Breath Res. (2013) 7:047102. 10.1088/1752-7155/7/4/047102
• Elliker KR Sommerville BA Broom DM Neal DE Armstrong S Williams HC. Key considerations for the experimental training and evaluation of cancer odour detection dogs: lessons learnt from a double-blind, controlled trial of prostate cancer detection. BMC Urol. (2014) 14:22. 10.1186/1471-2490-14-22 24575737
• Guest CM Harris R Anjum I Concha AR Rooney NJ. A lesson in standardization – Subtle aspects of the processing of samples can greatly affect dogs’ learning. Front Vet Sci. (2020) 7:525. 10.3389/fvets.2020.00525 33015138
• DeChant MT Bunker PC Hall NJ. Stimulus control of odorant concentration: pilot study of generalization and discrimination of odor concentration in canines. Animals. (2021) 11:326. 10.3390/ani11020326 33525503
• Wilson C Morant S Kane S Pesterfield C Guest C Rooney NJ. An owner-independent investigation of diabetes alert dog performance. Front Vet Sci. (2019) 6:91. 10.3389/fvets.2019.00091 30972346
• LoGrippo GA. Investigations of the use of beta-propiolactone in virus inactivation. Ann N Y Acad Sci. (1960) 83:578–94. 10.1111/j.1749-6632.1960.tb40931.x 14417982
• LoGrippo GA Hartman FW. Antigenicity of beta-propiolactone-inactivated virus vaccines. J Immunol. (1955) 75:123–8.
• Budowsky E Friedman E Zheleznova N Noskov F. Principles of selective inactivation of viral genome. VI. Inactivation of the infectivity of the influenza virus by the action of β-propiolactone. Vaccine. (1991) 9:398–402. 10.1016/0264-410X(91)90125-P
• Budowsky EI Smirnov YA Shenderovich SF. Principles of selective inactivation of viral genome. VIII. The influence of β-propiolactone on immunogenic and protective activities of influenza virus. Vaccine. (1993) 11:343–8. 10.1016/0264-410X(93)90197-6
• Chowdhury P Topno R Khan SA Mahanta J. Comparison of β -propiolactone and formalin inactivation on antigenicity and immune response of West Nile virus. Adv Virol. (2015) 2015:616898. 10.1155/2015/616898 26413092
• Gao Q Bao L Mao H Wang L Xu K Yang M et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science. (2020) 369:77–81. 10.1126/science.abc1932 32376603
• Lei S Gao X Sun Y Yu X Zhao L. Gas chromatography-mass spectrometry method for determination of β-propiolactone in human inactivated rabies vaccine and its hydrolysis analysis. J Pharm Anal. (2018) 8:373–7. 10.1016/j.jpha.2018.06.003 30595943
• Uittenbogaard JP Zomer B Hoogerhout P Metz B. Reactions of β-propiolactone with nucleobase analogues, nucleosides, and peptides. J Biol Chem. (2011) 286:36198–214. 10.1074/jbc.M111.279232 21868382
• Determann H Joachim H-U. Zur reaktion von ß-propiolacton mit semmproteinen und aminosäurederivaten. Z klin Chem Klin Biochem. (1971) 9:398–401.
• Lelie PN Reesink HW Lucas CJ. Inactivation of 12 viruses by heating steps applied during manufacture of a hepatitis B vaccine. J Med Virol. (1987) 23:297–301. 10.1002/jmv.1890230313 2828525
• Darnell MER Subbarao K Feinstone SM Taylor DR. Inactivation of the coronavirus that induces severe acute respiratory syndrome, SARS-CoV. J Virol Methods. (2004) 121:85–91. 10.1016/j.jviromet.2004.06.006 15350737
• Saluzzo JF Leguenno B Van der Groen G. Use of heat inactivated viral haemorrhagic fever antigens in serological assays. J Virol Methods. (1988) 22:165–72. 10.1016/0166-0934(88)90099-7
• Edwards S. Survival and inactivation of classical swine fever virus. Vet Microbiol. (2000) 73:175–81. 10.1016/S0378-1135(00)00143-7
• Leclercq I Batéjat C Burguière AM Manuguerra J. Heat inactivation of the Middle East respiratory syndrome coronavirus. Influenza Other Respir Viruses. (2014) 8:585–6. 10.1111/irv.12261 25074677
• Cutts T Grolla A Jones S Cook BWM Qiu X Theriault SS. Inactivation of Zaire ebolavirus variant makona in human serum samples analyzed by enzyme-linked immunosorbent assay. J Infect Dis. (2016) 214:S218–21. 10.1093/infdis/jiw289 27571899
• Park SL Huang Y-JS Hsu W-W Hettenbach SM Higgs S Vanlandingham DL. Virus-specific thermostability and heat inactivation profiles of alphaviruses. J Virol Methods. (2016) 234:152–5. 10.1016/j.jviromet.2016.04.004 27079828
• Abraham JP Plourde BD Cheng L. Using heat to kill SARS-CoV-2. Rev Med Virol. (2020) 30:e2115. 10.1002/rmv.2115 32614102
• Batéjat C Grassin Q Manuguerra J-C Leclercq I. Heat inactivation of the severe acute respiratory syndrome coronavirus 2. J Biosaf Biosecur. (2021) 3:1–3. 10.1016/j.jobb.2020.12.001 33521591
• Heßling M Hönes K Vatter P Lingenfelder C. Ultraviolet irradiation doses for coronavirus inactivation – Review and analysis of coronavirus photoinactivation studies. GMS Hyg Infect Control. (2020) 15:Doc08. 10.3205/dgkh000343 32547908
• Qiao Y Yang M Marabella IA McGee DAJ Aboubakr H Goyal S et al. Greater than 3-log reduction in viable coronavirus aerosol concentration in ducted ultraviolet-C (UV–C) systems. Environ Sci Technol. (2021) 55:4174–82. 10.1021/acs.est.0c05763 33263988
• Biasin M Bianco A Pareschi G Cavalleri A Cavatorta C Fenizia C et al. UV-C irradiation is highly effective in inactivating SARS-CoV-2 replication. Sci Rep. (2021) 11:6260. 10.1038/s41598-021-85425-w 33737536
• Budowsky EI Bresler SE Friedman EA Zheleznova NV. Principles of selective inactivation of viral genome. Arch Virol. (1981) 68:239–47. 10.1007/BF01314577 7271457
• Perdiz D Gróf P Mezzina M Nikaido O Moustacchi E Sage E. Distribution and repair of bipyrimidine photoproducts in solar UV-irradiated mammalian cells. J Biol Chem. (2000) 275:26732–42. 10.1016/S0021-9258(19)61437-7
• Browne K. Brought to light: how ultraviolet disinfection can prevent the nosocomial transmission of COVID-19 and other infectious diseases. Appl Microbiol. (2021) 1:537–56. 10.3390/applmicrobiol1030035
• Yao H Feilberg A. Characterisation of photocatalytic degradation of odorous compounds associated with livestock facilities by means of PTR-MS. Chem Eng J. (2015) 277:341–51. 10.1016/j.cej.2015.04.094
• Yang X Koziel JA Laor Y Zhu W van Leeuwen J Jenks WS et al. VOC removal from manure gaseous emissions with UV photolysis and UV-TiO2 photocatalysis. Catalysts. (2020) 10:607. 10.3390/catal10060607
• Lee M Koziel JA Murphy W Jenks WS Chen B Li P et al. Evaluation of TiO2 based photocatalytic treatment of odor and gaseous emissions from swine manure with UV-A and UV-C. Animals. (2021) 11:1289. 10.3390/ani11051289 33946294
• Lee M Koziel JA Murphy W Jenks WS Chen B Li P et al. Mitigation of odor and gaseous emissions from swine barn with UV-A and UV-C photocatalysis. Atmosphere. (2021) 12:585. 10.3390/atmos12050585
• Fletcher DB. Successful UV/oxidation of VOC-contaminated groundwater. Remediat J. (1991) 1:353–7. 10.1002/rem.3440010310
• Sekiguchi K Morinaga W Sakamoto K Tamura H Yasui F Mehrjouei M et al. Degradation of VOC gases in liquid phase by photocatalysis at the bubble interface. Appl Catal B Environ. (2010) 97:190–7. 10.1016/j.apcatb.2010.03.039
• Aboubakr HA Sharafeldin TA Goyal SM. Stability of SARS-CoV-2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: a review. Transbound Emerg Dis. (2021) 68:296–312. 10.1111/tbed.13707 32603505
• Horowitz B Lazo A Grossberg H Page G Lippin A Swan G. Virus inactivation by solvent/detergent treatment and the manufacture of SD-plasma. Vox Sang. (1998) 74:203–6. 10.1111/j.1423-0410.1998.tb05473.x 9789529
• Hellstern P. Solvent/detergent-treated plasma: composition, efficacy, and safety. Curr Opin Hematol. (2004) 11:346–50. 10.1097/01.moh.0000137915.88478.23
• Scheller C Krebs F Minkner R Astner I Gil-Moles M Wätzig H. Physicochemical properties of SARS-CoV-2 for drug targeting, virus inactivation and attenuation, vaccine formulation and quality control. Electrophoresis. (2020) 41:1137–51. 10.1002/elps.202000121 32469436
• Biesert L Suhartono H. Solvent/detergent treatment of human plasma – A very robust method for virus inactivation. Validated virus safety of OCTAPLAS®. Vox Sang. (1998) 74:207–12. 10.1111/j.1423-0410.1998.tb05474.x 9789530
• Ji H. Lysis of cultured cells for immunoprecipitation. Cold Spring Harb Protoc. (2010) 2010:pdb.prot5466. 10.1101/pdb.prot5466 20679375
• Olsen E Nielsen F. Predicting vapour pressures of organic compounds from their chemical structure for classification according to the VOCDirective and risk assessment in general. Molecules. (2001) 6:370–89. 10.3390/60400370
• Smither SJ Eastaugh LS Findlay JS Lever MS. Experimental aerosol survival of SARS-CoV-2 in artificial saliva and tissue culture media at medium and high humidity. Emerg Microbes Infect. (2020) 9:1415–7. 10.1080/22221751.2020.1777906 32496967
• Kwon T Gaudreault NN Richt JA. Seasonal stability of SARS-CoV-2 in biological fluids. Pathogens. (2021) 10:540. 10.3390/pathogens10050540 33946190
• van Doremalen N Bushmaker T Morris DH Holbrook MG Gamble A Williamson BN et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. (2020) 382:1564–7. 10.1056/NEJMc2004973 32182409
• Kasloff SB Leung A Strong JE Funk D Cutts T. Stability of SARS-CoV-2 on critical personal protective equipment. Sci Rep. (2021) 11:984. 10.1038/s41598-020-80098-3 33441775
• Perrin TE Rasmussen LEL Gunawardena R Rasmussen RA. A method for collection, long-term storage, and bioassay of labile volatile chemosignals. J Chem Ecol. (1996) 22:207–21. 10.1007/BF02055093 24227404
• Hsieh C-C Horng S-H Liao P-N. Stability of trace-level volatile organic compounds stored in canisters and tedlar bags. Aerosol Air Qual Res. (2003) 3:17–28. 10.4209/aaqr.2003.06.0003
• Miller TC Morgera SD Saddow SE Takshi A Palm M. Electronic nose with detection method for alcohol, acetone, and carbon monoxide in coronavirus disease 2019 breath simulation model. IEEE Sens J. (2021) 21:15935–43. 10.1109/JSEN.2021.3076102 35789085
• Caprio J. Electrophysiological distinctions between the taste and smell of amino acids in catfish. Nature. (1977) 266:850–1. 10.1038/266850a0 865608
• Caprio J. Olfaction and taste in the channel catfish: an electrophysiological study of the responses to amino acids and derivatives. J Comp Physiol. (1978) 123:357–71. 10.1007/BF00656970
• Caprio J Byrd RP. Electrophysiological evidence for acidic, basic, and neutral amino acid olfactory receptor sites in the catfish. J Gen Physiol. (1984) 84:403–22. 10.1085/jgp.84.3.403 6481334
• Nikonov AA Caprio J. Highly specific olfactory receptor neurons for types of amino acids in the channel catfish. J Neurophysiol. (2007) 98:1909–18. 10.1152/jn.00548.2007 17686913
• Nikonov AA Caprio J. Responses of olfactory forebrain units to amino acids in the channel catfish. J Neurophysiol. (2007) 97:2490–8. 10.1152/jn.01198.2006 17251362
• Naim M Schutz O Zehavi U Rouseff RL Haleva-Toledo E. Effects of orange juice fortification with thiols on p -vinylguaiacol formation, ascorbic-acid degradation, browning, and acceptance during pasteurization and storage under moderate conditions. J Agric Food Chem. (1997) 45:1861–7. 10.1021/jf9608884
• Laska M. Olfactory perception of 6 amino acids by human subjects. Chem Senses. (2010) 35:279–87. 10.1093/chemse/bjq017 20190007
• Halpern M. The organization and function of the vomeronasal system. Annu Rev Neurosci. (1987) 10:325–62. 10.1146/annurev.ne.10.030187.001545 3032065
• Keverne EB. The vomeronasal organ. Science. (1999) 286:716–20. 10.1126/science.286.5440.716 10531049
• Karim SSA Karim QA. Omicron SARS-CoV-2 variant: a new chapter in the COVID-19 pandemic. Lancet. (2021) 398:2126–8. 10.1016/S0140-6736(21)02758-6
• Tao K Tzou PL Nouhin J Gupta RK de Oliveira T Kosakovsky Pond SL et al. The biological and clinical significance of emerging SARS-CoV-2 variants. Nat Rev Genet. (2021) 22:757–73. 10.1038/s41576-021-00408-x 34535792
• Murarka M Vesley-Gross ZI Essler JL Smith PG Hooda J Drapkin R et al. Testing ovarian cancer cell lines to train dogs to detect ovarian cancer from blood plasma: a pilot study. J Vet Behav. (2019) 32:42–8. 10.1016/j.jveb.2019.04.010
• Ciurkiewicz M Armando F Schreiner T de Buhr N Pilchová V Krupp-Buzimikic V et al. Ferrets are valuable models for SARS-CoV-2 research. Vet Pathol. (2022) 59:661–72. 10.1177/03009858211071012 35001763
• Paul-Ehrlich-Institut. Mindestkriterien für SARS-CoV-2 Antigentests im Sinne von §1 Abs. 1 Satz 1 TestVO: Antigenschnelltests. (2022). Available online at: https://www.pei.de/SharedDocs/Downloads/DE/newsroom/dossiers/mindestkriterien-sars-cov-2-antigentests.pdf?__blob=publicationFile&v=9 (accessed May 1, 2022).
• FAO, OIE, WHO, UNEP. Joint Tripartite (FAO, OIE, WHO) and UNEP Statement Tripartite and UNEP Support OHHLEP’s Definition of “One Health”. (2022). Available online at: https://wedocs.unep.org/bitstream/handle/20.500.11822/37600/JTFOWU.pdf (accessed May 5, 2022).
• Aleta A Martín-Corral D Pastore y Piontti A Ajelli M Litvinova M Chinazzi M et al. Modelling the impact of testing, contact tracing and household quarantine on second waves of COVID-19. Nat Hum Behav. (2020) 4:964–71. 10.1038/s41562-020-0931-9 32759985
• WHO. COVID-19 Strategic Preparedness and Response Plan (SPRP 2021). (2022). Available online at: https://www.who.int/publications-detail-redirect/WHO-WHE-2021.02 (accessed April 10, 2022).
• Dai T Zaman MH Padula WV Davidson PM. Supply chain failures amid COVID-19 signal a new pillar for global health preparedness. J Clin Nurs. (2021) 30:e1–3. 10.1111/jocn.15400 32620038
• Jayamohan H Lambert CJ Sant HJ Jafek A Patel D Feng H et al. SARS-CoV-2 pandemic: a review of molecular diagnostic tools including sample collection and commercial response with associated advantages and limitations. Anal Bioanal Chem. (2021) 413:49–71. 10.1007/s00216-020-02958-1 33073312
• Vandenberg O Martiny D Rochas O van Belkum A Kozlakidis Z. Considerations for diagnostic COVID-19 tests. Nat Rev Microbiol. (2021) 19:171–83. 10.1038/s41579-020-00461-z 33057203
• EC. EU Guidance on Operating Procedures for Explosive Detection Dogs in Public Spaces. (2022). Available online at: https://ec.europa.eu/newsroom/pps/items/696384 (accessed May 1, 2022).