• Irina Georgieva National Reference Laboratory "Enteroviruses”, Department of Virology, National Centre of Infectious and Parasitic Diseases, Sofia, Bulgaria Author
  • Asya Stoyanova National Reference Laboratory "Enteroviruses”, Department of Virology, National Centre of Infectious and Parasitic Diseases Author
  • Svetla Angelova National Reference Laboratory "Influenza and ARD”, Department of Virology, National Centre of Infectious and Parasitic Diseases, Author
  • Savina Stoitsova Department of Epidemiology, National Centre of Infectious and Parasitic Diseases Author
  • Silvia Voleva National Reference Laboratory "Influenza and ARD”, Department of Virology, National Centre of Infectious and Parasitic Diseases, Author
  • Neli Korsun National Reference Laboratory "Influenza and ARD”, Department of Virology, National Centre of Infectious and Parasitic Diseases, Author
  • Lubomira Nikolaeva-Glomb National Reference Laboratory "Enteroviruses”, Department of Virology, National Centre of Infectious and Parasitic Diseases Author



rhinovirus, common cold, bronchiolitis, asthma


Acute respiratory infections cause significant morbidity and mortality even before the COVID-19 pandemic. Pandemic restrictions decreased circulation of many respiratory viruses but some less troubling infections such as common cold are still circulating.

One of the most frequent causative agents of common cold are rhinoviruses. The fact that these pathogens have been able to slip through anti-COVID preventive measures raises the question of whether we really know this group of viruses and whether these viruses cause only common cold. The clinical impact of rhinoviruses seems to be underestimated.

In searching of an answer how rhinoviruses have slipped through the anti-COVID precautions we referred to the work of infectious disease specialists, virologists and epidemiologists -much of it conducted decades before the current pandemic. A non-systematic search of the literature is performed. Some of the latest findings on rhinoviruses along with basic knowledge on their biology and clinical impact are summarized in this review.


Download data is not yet available.


Makela MJ, Puhakka T, Ruuskanen O, Leinonen M, Saikku P, Kimpimaki M, Blomqvist S, Hyypia T, Arstila P. Viruses and Bacteria in the Etiology of the Common Cold. J Clin Microbiol. 1998; 36: 539–542. DOI:

Brownlee JW, Turner RB. New developments in the epidemiology and clinical spectrum of rhinovirus infections. Curr Opin Pediatr. 2008; 20(1):67-71. DOI:

Fendrick AM, Monto AS, Nightengale B, Sarnes M. The Economic Burden of Non–Influenza-Related Viral Respiratory Tract Infection in the United States. Arch Intern Med. 2003; 163(4):487–494. DOI:

Hayden FG. Rhinovirus and the lower respiratory tract. Rev Med Virol. 2004; 14(1):17-31. DOI:

Thibaut HJ, Lacroix C, De Palma AM, Franco D, Decramer M, Neyts J. Toward antiviral therapy/prophylaxis for rhinovirus-induced exacerbations of chronic obstructive pulmonary disease: challenges, opportunities, and strategies. Rev Med Virol. 2016; 26(1):21–33. DOI:

Gern JE, Busse WW. Association of rhinovirus infections with asthma. Clin Microbiol Rev.1999; 12(1):9–18. DOI:

McManus TE, Marley AM, Baxter N, Christie SN, O'Neill HJ, Elborn JS, Coyle PV, Kidney JC. Respiratory viral infection in exacerbations of COPD. Respir Med. 2008; 102(11):1575-80. DOI:

Gern JE. The ABCs of rhinoviruses, wheezing, and asthma. J Virol. 2010; 84(15):7418–7426. DOI:

Papadopoulos NG. Bates PJ, Bardin PG, Papi A, Leir S, Fraenkel DJ, Meyer J, Lackie PM, Sanderson G, Holgate ST, Johnston SL. Rhinoviruses Infect the Lower Airways. The Journal of Infectious Diseases. 2000; 181(6):1875–1884. DOI:

Gutman JA, Peck AJ, Kuypers J, Boeckh M. Rhinovirus as a cause of fatal lower respiratory tract infection in adult stem cell transplantation patients: a report of two cases. Bone Marrow Transplantation. 2007; 40:809-811. DOI:

Gavala ML, Bertics PJ, and Gern JE. Rhinoviruses, allergic inflammation, and asthma. Immunol Rev 2011; 242(1):69-90. DOI:

Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, Printz MC, Lee W-M, Shult PA, Reisdorf E, Carlson-Dakes KT, Salazar LP, DaSilva DF, Tisler CJ, Gern JE, Lemansake Jr RF. Wheezing Rhinovirus Illnesses in Early Life Predict Asthma Development in High-Risk Children. Am J Respir Crit Care Med. 2008; 178(7):667-72. DOI:

Kenealy T, Arroll B. Antibiotics for the common cold and acute purulent rhinitis. Cochrane Database Syst Rev. 2013;6: doi:10.1002/14651858.CD000247.pub3. DOI:

Arden KE, McErlean P, Nissen MD, Sloots TP, Mackay IM. Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections. J Med Virol. 2006; 78(9):1232‐1240. DOI:

Kaiser L, Aubert JD, Pache JC, Deffernez C, Rochat T, Garbino J, Wunderli W, Meylan P, Yerly S, Perrin L, Letovanec I, Nicod L, Tapparel C, Soccal PM. Chronic rhinoviral infection in lung transplant recipients. Am J Respir Crit Care Med. 2006;174(12):1392–1399. DOI:

Lee WM, Kiesner C, Pappas T, Lee I, Grindle K, Jartti T, Jakiela B, Lemanske Jr RF, Shult PA, Gern JE. A diverse group of previously unrecognized human rhinoviruses are common causes of respiratory illnesses in infants. PloS One. 2007; 2(10):e966. DOI:

McIntyre CL, Knowles NJ, Simmonds P. Proposals for the classification of human rhinovirus species A, B and C into genotypically assigned types. J Gen Virol. 2013;94(Pt 8):1791–1806. DOI:

Bochkov YA, Watters K, Ashraf S, Griggs TF, Devries MK, Jackson DJ, Palmenberg AC, Gern JE. Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication. Proc Natl Acad Sci USA. 2015; 112(17):5485–5490. DOI:

Bochkov YA, Palmenberg AC, Lee WM, Rathe JA, Amineva SP, Sun X, Pasic TR, Jarjour NN, Liggett SB, Gern JE. Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. Nat Med. 2011;17(5):627-632. DOI:

Simmonds P, Gorbalenya AE, Harvala H, Hovi T, Knowles NJ, Lindberg AM, Oberste MS, Palmenberg AC, Reuter G, Skern T, Tapparel C, Wolthers KC, Woo PCY, Zell R. Recommendations for the nomenclature of enteroviruses and rhinoviruses. Arch Virol. 2020;165(3):793-797. DOI:

Greenberg SB. Respiratory consequences of rhinovirus infection. Arch Intern Med. 2003;163(3);278–284. DOI:

Hendry E, Hatanaka H, Fry E, Smyth M, Tate J, Stanway G, Santti J, Maaronen M, Hyypiä T, Stuart D. The crystal structure of coxsackievirus A9: new insights into the uncoating mechanisms of enteroviruses. Structure (London, England:1993).1999; 7(12):1527–1538. DOI:

Rossmann MG, He Y and Kuhn RJ. Picornavirus-receptor interactions. Trends Microbiol. 2002; 10(7):324–331. DOI:

Hayden FG, Herrington DT, Coats TL, Kim K, Cooper EC, Villano SA, Liu S, Hudson S, Pevear DC, Collett M, McKinlay M, Pleconaril Respiratory Infection Study Group. Efficacy and safety of oral pleconaril for treatment of colds due to picornaviruses in adults: results of 2 double-blind, randomized, placebo-controlled trials. Clin Infect Dis. 2003; 36(12):1523–1532. DOI:

McKinlay MA. WIN 51711, a new systematically active broad-spectrum antipicornavirus agent. J Antimicrob Chemother. 1985;16(3): 284–286. DOI:

Liu Y, Hill MG, Klose T, Chen Z, Watters K, Bochkov YA, Jiang W, Palmenberg AC, Rossmann MG. Atomic structure of a rhinovirus C, a virus species linked to severe childhood asthma. Proc Natl Acad Sci USA. 2016; 113(32):8997-9002. DOI:

Borman AM, Bailly JL, Girard M, Kean KM. Picornavirus internal ribosome entry segments: comparison of translation efficiency and the requirements for optimal internal initiation of translation in vitro. Nucleic Acids Res.1995; 23(18):3656–3663. DOI:

Paul AV and Wimmer E. Initiation of protein-primed picornavirus RNA synthesis. Virus Res.2015;206:12–26. DOI:

Uncapher CR, DeWitt CM, Colonno RJ. The major and minor group receptor families contain all but one human rhinovirus serotype. Virology. 1991;180(2):814‐817. DOI:

Palmenberg AC, Rathe JA, Liggett SB. Analysis of the complete genome sequences of human rhinovirus. J Allergy Clin Immunol. 2010;125(6):1190‐1201. DOI:

Verdaguer N, Fita I, Reithmayer M, Moser R, Blaas D. X-ray structure of a minor group human rhinovirus bound to a fragment of its cellular receptor protein. Nat Struct Mol Biol. 2004;11(5):429–434. DOI:

Jacobs SE, Lamson DM, George KSt, Walsh TJ. Human rhinoviruses. Clin Microbiol Rev. 2013; 26(1):135–162. DOI:

Fuchs R and Blaas D. Uncoating of human rhinoviruses. Rev Med Virol. 2010;20(5):281–297. DOI:

Baggen J, Thibaut HJ, Strating J, van Kuppeveld F. The life cycle of non-polio enteroviruses and how to target it. Nat Rev Microbiol. 2018;16(6): 368–381. DOI:

Rowlands DJ. Picornaviruses. In: eLS, John Wiley & Sons, Ltd (Ed.). 2015, doi:10.1002/9780470015902.a0001080.pub3. DOI:

van der Schaar HM, Dorobantu CM, Albulescu L, Strating J, van Kuppeveld F. Fat(al) attraction: Picornaviruses Usurp Lipid Transfer at Membrane Contact Sites to Create Replication Organelles. Trends Microbiol. 2016; 24(7):535–546. DOI:

Inal JM, Jorfi S. Coxsackievirus B transmission and possible new roles for extracellular vesicles. Biochem Soc Trans. 2013; 41(1):299–302. DOI:

Lai JK, Sam IC, Chan YF. The Autophagic Machinery in Enterovirus Infection. Viruses. 2016; 8(2):32. DOI:

Domingo E, Sheldon J, Perales C. Viral quasispecies evolution. Microbiol Mol Biol Rev. 2012; 76(2):159-216. DOI:

Royston L, Tapparel C. Rhinoviruses and Respiratory Enteroviruses: Not as Simple as ABC. Viruses. 2016; 8(1):16. DOI:

Lukashev AN, Lashkevich VA, Ivanova OE, Koroleva GA, Hinkkanen AE, Ilonen J. Recombination in circulating Human enterovirus B: independent evolution of structural and non-structural genome regions. J Gen Virol. 2005; 86(Pt 12):3281–3290. DOI:

Santti J, Hyypiä T, Kinnunen L, Salminen M. Evidence of recombination among enteroviruses. J Virol, 1999; 73(10): 8741–8749. DOI:

Simmonds P, Welch J. Frequency and dynamics of recombination within different species of human enteroviruses. J Virol. 2006; 80(1):483–493. DOI:

McIntyre CL, McWilliam Leitch EC, Savolainen-Kopra C, Hovi T, Simmonds P. Analysis of genetic diversity and sites of recombination in human rhinovirus species C. J Virol. 2010; 84(19):10297–10310. DOI:

Tapparel C, Junier T, Gerlach D, Van-Belle S, Turin L, Cordey S, Mühlemann K, Regamey N, Aubert JD, Soccal PM, Eigenmann P, Zdobnov E, Kaiser L. New respiratory enterovirus and recombinant rhinoviruses among circulating picornaviruses. Emerg Infect Dis. 2009;15(5):719–726. DOI:

L'Huillier AG, Tapparel C, Turin L, Boquete-Suter P, Thomas Y, Kaiser L. Survival of rhinoviruses on human fingers. Clin Microbiol Infect. 2015; 21(4): 381–385. DOI:

Fox JP, Cooney MK, Hall CE. The Seattle virus watch. V. Epidemiologic observations of rhinovirus infections, 1965-1969, in families with young children. Am J Epidemiol. 1975;101(2):122–143. DOI:

Fox JP, Cooney MK, Hall CE, Foy HM. Rhinoviruses in Seattle families, 1975-1979. Am J Epidemiol. 1985;122(5):830–846. DOI:

Foxman EF, Storer JA, Fitzgerald ME, Wasik BR, Hou L, Zhao H, Turner PE, Pyle AM, Iwasaki A. Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells. Proc Natl Acad Sci USA. 2015;112(3):827–832. DOI:

Papadopoulos NG, Sanderson G, Hunter J, Johnston SL. Rhinoviruses replicate effectively at lower airway temperatures. J Med Virol. 1999; 58(1):100–104. DOI:<100::AID-JMV16>3.0.CO;2-D

Tapparel C, Sobo K, Constant S, Huang S, Van Belle S, Kaiser L. Growth and characterization of different human rhinovirus C types in three-dimensional human airway epithelia reconstituted in vitro. Virology. 2013; 446(1-2):1–8. DOI:

Pitkäranta A, Arruda E, Malmberg H, Hayden FG. Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR. J Clin Microbiol, 1997; 35(7): 1791–1793. DOI:

Chantzi FM, Papadopoulos NG, Bairamis T, Tsiakou M, Bournousouzis N, Constantopoulos AG, Liapi G, Xatzipsalti M, Kafetzis DA. Human rhinoviruses in otitis media with effusion. Pediatr Allergy Immunol. 2006; 17(7):514–518. DOI:

Lupo J, Schuffenecker I, Morel-Baccard C, Bardet J, Payen V, Kaiser L, Constant S, Lobrinus JA, Lin-Marq N, Lina B, Morand P, Tapparel C. Disseminated rhinovirus C8 infection with infectious virus in blood and fatal outcome in a child with repeated episodes of bronchiolitis. J Clin Microbiol, 2015; 53(5): 1775–1777. DOI:

Harvala H, McIntyre CL, McLeish NJ, Kondracka J, Palmer J, Molyneaux P, Gunson R, Bennett S, Templeton K, Simmonds P. High detection frequency and viral loads of human rhinovirus species A to C in fecal samples; diagnostic and clinical implications. J Med Virol. 2012; 84(3):536–542. DOI:

Esposito S, Daleno C, Scala A, Castellazzi L, Terranova L, Sferrazza Papa S, Longo MR, Pelucchi C, Principi N. Impact of rhinovirus nasopharyngeal viral load and viremia on severity of respiratory infections in children. Eur J Clin Microbiol Infect Dis. 2014; 33(1):41–48. DOI:

Urquhart GE, Stott EJ. Rhinoviraemia. BMJ. 1970; 4(5726): 28–30. DOI:

Honkanen H, Oikarinen S, Peltonen P, Simell O, Ilonen J, Veijola R, Knip M, Hyöty H. Human rhinoviruses including group C are common in stool samples of young Finnish children. J Clin Virol. 2013; 56(3): 250–254. DOI:

Sajjan U, Wang Q, Zhao Y, Gruenert DC, Hershenson MB. Rhinovirus disrupts the barrier function of polarized airway epithelial cells. Am J Respir Crit Care Med. 2008;178(12):1271–1281. DOI:

Lambrecht BN, Hammad H. Allergens and the airway epithelium response: gateway to allergic sensitization. J Allergy Clin Immunol. 2014; 134(3): 499–507. DOI:

Lambrecht BN, Hammad H. Asthma: the importance of dysregulated barrier immunity. Eur J Immunol. 2013; 43(12): 3125–3137. DOI:

Turner RB. 177 – Rhinovirus. In Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Eighth Edition), Elsevier Inc. 2015; 2113-2121. DOI:

Barclay WS, al-Nakib W, Higgins PG, Tyrrell DA. The time course of the humoral immune response to rhinovirus infection. Epidemiology and infection.1989;103(3):659–669. DOI:

Steinke JW, Liu L, Turner RB, Braciale TJ, Borish L. Immune surveillance by rhinovirus-specific circulating CD4+ and CD8+ T lymphocytes. PloS One. 2015;10(1):e0115271. DOI:

van Benten I, Koopman L, Niesters B, Hop W, van Middelkoop B, de Waal L, van Drunen K, Osterhaus A, Neijens H, Fokkens W. Predominance of rhinovirus in the nose of symptomatic and asymptomatic infants. Pediatr Allergy Immunol. 2003; 14(5): 363–370. DOI:

Jansen RR, Wieringa J, Koekkoek SM, Visser CE, Pajkrt D, Molenkamp R, de Jong MD, Schinkel J. Frequent detection of respiratory viruses without symptoms: toward defining clinically relevant cutoff values. J Clin Microbiol. 2011; 49(1):2631–2636. DOI:

Jartti T, Jartti L, Peltola V, Waris M, Ruuskanen O. Identification of respiratory viruses in asymptomatic subjects: asymptomatic respiratory viral infections. Pediatr Infect Dis J. 2008; 27(12):1103–1107. DOI:

Iwane MK, Prill MM, Lu X, Miller EK, Edwards KM, Hall CB, Griffin MR, Staat MA, Anderson LJ, Williams JV, Weinberg GA, Ali A, Szilagyi PG, Zhu Y, Erdman DD. Human rhinovirus species associated with hospitalizations for acute respiratory illness in young US children. J Infect Dis. 2011; 204(11):1702–1710. DOI:

Singleton RJ, Bulkow LR, Miernyk K, DeByle C, Pruitt L, Hummel KB, Bruden D, Englund JA, Anderson LJ, Lucher L, Holman RC, Hennessy TW. Viral respiratory infections in hospitalized and community control children in Alaska. J Med Virol. 2010; 82(7):1282–1290. DOI:

Graat JM, Schouten EG, Heijnen ML, Kok FJ, Pallast EG, de Greeff SC, Dorigo-Zetsma JW. A prospective, community-based study on virologic assessment among elderly people with and without symptoms of acute respiratory infection. J Clin Epidemiol. 2003; 56(12):1218–1223. DOI:

Turner RB. Epidemiology, pathogenesis, and treatment of the common cold. Ann Allergy Asthma Immunol. 1997; 78(6):531–540. DOI:

Pappas DE, Hendley JO, Hayden FG, Winther B. Symptom profile of common colds in school-aged children. Pediatr Infect Dis J. 2008; 27(1):8–11. DOI:

Gwaltney JMJ, Hendley JO, Patrie JT. Symptom severity patterns in experimental common colds and their usefulness in timing onset of illness in natural colds. Clin Infect Dis. 2003; 36(6):714–723. DOI:

Armengol CE, Hendley JO, Winther B. Occurrence of acute otitis media during colds in children younger than four years. Pediatr Infect Dis J. 2011; 30(6):518–520. DOI:

Marom T, Nokso-Koivisto J, Chonmaitree T. Viral-bacterial interactions in acute otitis media. Curr Allergy Asthma Rep. 2012; 12(6): 551–558. DOI:

Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang dY, Wormald PJ. European Position Paper on Rhinosinusitis and Nasal Polyps. Rhinol Suppl.2012; 23:3–298.

Welge-Lüssen A, Wolfensberger M. Olfactory disorders following upper respiratory tract infections. Adv Otorhinolaryngol. 2006; 63:125–132. DOI:

Papadopoulos NG. Do rhinoviruses cause pneumonia in children?. Paediatr Respir Rev. 5 Suppl A. 2004; S191–S195. DOI:

Ghosh S, Champlin R, Couch R, Englund J, Raad I, Malik S, Luna M, Whimbey E. Rhinovirus infections in myelosuppressed adult blood and marrow transplant recipients. Clin Infect Dis.1999; 29(3):528–532. DOI:

National Asthma Education and Prevention Program, Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report. 2007. J Allergy Clin Immunol. 2007; 120(5 Suppl), p. S94–S138. DOI:

Hammond C, Kurten M, Kennedy JL. Rhinovirus and asthma: a storied history of incompatibility. Curr Allergy Asthma Rep. 2015; 15(2):502. DOI:

Stone CA, and Miller EK. Understanding the Association of Human Rhinovirus with Asthma. Clin Vaccine Immunol. 2015; 23(1):6–10. DOI:

Versalovic J, Caroll KC, Funke G, Jorgensen JH, Landry ML, Warnock DW. Manual of clinical microbiology. ASM Press, ©2011, Washington, D.C. DOI:

Georgieva I, Galabov A. In Vitro Anti-Rhinovirus Activity of Some Picornavirus Replication Inhibitors. Acta microbiologica Bulgarica, 2016; 32: 237-242.

Mello C, Aguayo E, Rodriguez M, Lee G, Jordan R, Cihlar T, Birkus G. Multiple classes of antiviral agents exhibit in vitro activity against human rhinovirus type C. Antimicrob Agents Chemother. 2014;58(3):1546–1555. DOI:

Choi HJ. In Vitro Antiviral Activity of Sakuranetin against Human Rhinovirus 3. Osong Public Health Res Perspect. 2017; 8(6): 415–420. DOI:

De Sutter AI, Saraswat A, van Driel ML. Antihistamines for the common cold. Cochrane Database Syst Rev. 2015; 11:CD009345. DOI:

Savolainen-Kopra C, Korpela T, Simonen-Tikka ML, Amiryousefi A, Ziegler T, Roivainen M, Hovi T. Single treatment with ethanol hand rub is ineffective against human rhinovirus--hand washing with soap and water removes the virus efficiently. J Med Virol. 2012; 84(3):543–547. DOI:

Sattar SA, Jacobsen H, Springthorpe VS, Cusack TM, Rubino JR. Chemical disinfection to interrupt transfer of rhinovirus type 14 from environmental surfaces to hands. Appl Environ Microbiol. 1993; 59(5): 1579–1585. DOI:

Glanville N, Johnston SL. Challenges in developing a cross-serotype rhinovirus vaccine. Curr Opin Virol. 2015;11:83–88. DOI:

Palmenberg AC, Spiro D, Kuzmickas R, Wang S, Djikeng A, Rathe JA, Fraser-Liggett CM, Liggett SB. Sequencing and analyses of all known human rhinovirus genomes reveal structure and evolution. Science . 2009; 324(5923):55–59. DOI:

McLean GR. Developing a vaccine for human rhinoviruses. Journal of vaccines & immunization. 2014; 2(3): 16–20. DOI:

L'Huillier AG, Kaiser L, Petty TJ, Kilowoko M, Kyungu E, Hongoa P, et al. Molecular epidemiology of human rhinoviruses and enteroviruses highlights their diversity in sub-Saharan Africa. Viruses. 2015;7:6412-23 DOI:

Panda S, Mohakud NK, Panda S, Kumar S. Epidemiology and phylogenetic analysis of human rhinovirus/Enterovirus in Odisha, Eastern India. Indian J Med Microbiol. 2019; 37:569-73 DOI:

Monto AS. The seasonality of rhinovirus infections and its implications for clinical recognition. Clinical Therapeutics. 2002; 24(12):1987-1997. DOI:







How to Cite

Georgieva, I.; Stoyanova, A.; Angelova, S.; Stoitsova, S.; Voleva, S.; Korsun, N.; Nikolaeva-Glomb, L. DO WE KNOW RHINOVIRUSES AND THEIR CLINICAL IMPACT?. Probl Infect Parasit Dis 2021, 49 (1), 5-12.

Most read articles by the same author(s)

1 2 > >>