Diagnostic Considerations

Studies document that patients are frequently infected with both bacterial and viral pathogens, making it impossible to rule out bacterial disease even when rapid viral test results are positive. Additionally, no unique identifying clinical characteristics are present that allow the physician to differentiate viral disease from bacterial disease in the emergency department (ED).

Although the most common cause of community-acquired pneumonia remains Streptococcus pneumoniae (a fact that may change with the increasing use of pneumococcal vaccines), in as many as 40-60% of patients with community-acquired pneumonia, the etiologic agent is not identified. Furthermore, convincing associations between the patient's symptoms, physical findings, laboratory test results, and specific etiologies are lacking.

Therefore, no way of accurately determining the etiology of pneumonia during the initial visit to the ED exists. Obtaining a chest radiograph in patients with suspected pneumonia is recommended, both to find complications, such as pleural effusions, and to discourage the use of antibiotics in healthy patients with bronchitis rather than pneumonia.

Influenza viruses are the most common cause of viral pneumonia in civilian adults. Influenza usually is seen in epidemics and pandemics. Influenza A is the serotype most frequently responsible for major epidemics and pandemics; it is the most frequent cause of viral pneumonia in adults.

Influenza epidemics occur during the winter months and are associated with significant morbidity and mortality. Patients with chronic obstructive pulmonary disease (COPD), heart failure, hemoglobinopathies, and immunosuppression are at increased risk for severe disease, which can lead to death. Influenza virus is transmitted from person to person primarily by droplet and aerosol exposure to the virus. The incubation period is 1-5 days after exposure.

Patients with high-grade fever, myalgias, and cough during the winter months should be suspected to have influenza. If test results are negative for influenza, RSV pneumonia should also be suspected during the winter in patients with coryza, wheezing, low-grade fever, and patchy infiltrates on chest radiographs. Because clinical features and periods of activity for many viruses overlap, laboratory confirmation of influenza is recommended for cases involving patients who are seriously ill or institutionalized.

Viral pathogens and host factors

Patient age and immune status can offer a clue to the possible etiology of viral pneumonia. The following viruses commonly cause pneumonia in children:

Respiratory syncytial virus
Influenza viruses A and B
Parainfluenza virus
Adenovirus
Human metapneumovirus
Coronavirus
Measles virus (in unvaccinated children)

The following viruses commonly cause pneumonia in immunocompetent adults:

Influenza viruses A and B
Adenovirus
Respiratory syncytial virus
Parainfluenza virus
Coronavirus
Varicella-zoster virus

The following viruses commonly cause pneumonia in immunocompromised hosts:

Cytomegalovirus
Herpes simplex virus
Influenza
Respiratory syncytial virus
Parainfluenza virus
Adenovirus
Varicella-zoster virus

Differential Diagnoses

Workup

Wald TG, Miller BA, Shult P, Drinka P, Langer L, Gravenstein S. Can respiratory syncytial virus and influenza A be distinguished clinically in institutionalized older persons?. J Am Geriatr Soc. 1995 Feb. 43(2):170-4. [QxMD MEDLINE Link].
Korppi M, Don M, Valent F, Canciani M. The value of clinical features in differentiating between viral, pneumococcal and atypical bacterial pneumonia in children. Acta Paediatr. 2008 Jul. 97(7):943-7. [QxMD MEDLINE Link].
Jennings LC, Anderson TP, Beynon KA, Chua A, Laing RT, Werno AM, et al. Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax. 2008 Jan. 63(1):42-8. [QxMD MEDLINE Link].
Marcos MA, Camps M, Pumarola T, et al. The role of viruses in the aetiology of community-acquired pneumonia in adults. Antivir Ther. 2006. Vol. 11:351-359.
Templeton KE, Scheltinga SA, van den Eeden WC, Graffelman AW, van den Broek PJ, Claas EC. Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction. Clin Infect Dis. 2005 Aug 1. 41(3):345-51. [QxMD MEDLINE Link].
Kim MA, Park JS, Lee CW, Choi WI. Pneumonia severity index in viral community acquired pneumonia in adults. PLoS One. 2019. 14 (3):e0210102. [QxMD MEDLINE Link]. [Full Text].
McLaren SH, Mistry RD, Neuman MI, Florin TA, Dayan PS. Guideline Adherence in Diagnostic Testing and Treatment of Community-Acquired Pneumonia in Children. Pediatr Emerg Care. 2019 Feb 14. [QxMD MEDLINE Link].
Dugan VG, Blanton L, Elal AIA, et al. Update: Influenza Activity - United States, October 1-November 25, 2017. MMWR Morb Mortal Wkly Rep. 2017 Dec 8. 66 (48):1318-1326. [QxMD MEDLINE Link].
Almansa R, Martínez-Orellana P, Rico L, Iglesias V, Ortega A, Vidaña B, et al. Pulmonary transcriptomic responses indicate a dual role of inflammation in pneumonia development and viral clearance during 2009 pandemic influenza infection. PeerJ. 2017. 5:e3915. [QxMD MEDLINE Link].
Levy MM, Baylor MS, Bernard GR, Fowler R, Franks TJ, Hayden FG, et al. Clinical issues and research in respiratory failure from severe acute respiratory syndrome. Am J Respir Crit Care Med. 2005 Mar 1. 171(5):518-26. [QxMD MEDLINE Link].
Legg JP, Hussain IR, Warner JA, Johnston SL, Warner JO. Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med. 2003 Sep 15. 168(6):633-9. [QxMD MEDLINE Link].
Katsurada N, Suzuki M, Aoshima M, Yaegashi M, Ishifuji T, Asoh N, et al. The impact of virus infections on pneumonia mortality is complex in adults: a prospective multicentre observational study. BMC Infect Dis. 2017 Dec 6. 17 (1):755. [QxMD MEDLINE Link].
Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. 2006 Feb 15. 42(4):518-24. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Novel Coronavirus 2019. CDC. Available at https://www.cdc.gov/coronavirus/novel-coronavirus-2019.html. January 16, 2020; Accessed: January 17, 2020.
Shields AF, Hackman RC, Fife KH, Corey L, Meyers JD. Adenovirus infections in patients undergoing bone-marrow transplantation. N Engl J Med. 1985 Feb 28. 312(9):529-33. [QxMD MEDLINE Link].
Metzgar D, Osuna M, Kajon AE, Hawksworth AW, Irvine M, Russell KL. Abrupt emergence of diverse species B adenoviruses at US military recruit training centers. J Infect Dis. 2007 Nov 15. 196(10):1465-73. [QxMD MEDLINE Link].
Louie JK, Kajon AE, Holodniy M, Guardia-LaBar L, Lee B, Petru AM, et al. Severe pneumonia due to adenovirus serotype 14: a new respiratory threat?. Clin Infect Dis. 2008 Feb 1. 46(3):421-5. [QxMD MEDLINE Link].
Tate JE, Bunning ML, Lott L, Lu X, Su J, Metzgar D, et al. Outbreak of severe respiratory disease associated with emergent human adenovirus serotype 14 at a US air force training facility in 2007. J Infect Dis. 2009 May 15. 199(10):1419-26. [QxMD MEDLINE Link].
Lewis PF, Schmidt MA, Lu X, Erdman DD, Campbell M, Thomas A, et al. A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14. J Infect Dis. 2009 May 15. 199(10):1427-34. [QxMD MEDLINE Link].
Lewis VA, Champlin R, Englund J, Couch R, Goodrich JM, Rolston K, et al. Respiratory disease due to parainfluenza virus in adult bone marrow transplant recipients. Clin Infect Dis. 1996 Nov. 23(5):1033-7. [QxMD MEDLINE Link].
van den Hoogen BG, de Jong JC, Groen J, Kuiken T, de Groot R, Fouchier RA, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med. 2001 Jun. 7(6):719-24. [QxMD MEDLINE Link].
Falsey AR, Erdman D, Anderson LJ, Walsh EE. Human metapneumovirus infections in young and elderly adults. J Infect Dis. 2003 Mar 1. 187(5):785-90. [QxMD MEDLINE Link].
Boivin G, Abed Y, Pelletier G, Ruel L, Moisan D, Cote S, et al. Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups. J Infect Dis. 2002 Nov 1. 186(9):1330-4. [QxMD MEDLINE Link].
Cane PA, van den Hoogen BG, Chakrabarti S, Fegan CD, Osterhaus AD. Human metapneumovirus in a haematopoietic stem cell transplant recipient with fatal lower respiratory tract disease. Bone Marrow Transplant. 2003 Feb. 31(4):309-10. [QxMD MEDLINE Link].
Lau SK, Woo PC, Yip CC, Tse H, Tsoi HW, Cheng VC, et al. Coronavirus HKU1 and other coronavirus infections in Hong Kong. J Clin Microbiol. 2006 Jun. 44(6):2063-71. [QxMD MEDLINE Link]. [Full Text].
Luzzati R, D'Agaro P, Busca A, Maurel C, Martellani F, Rosin C, et al. Herpes simplex virus (HSV) pneumonia in the non-ventilated immunocompromised host: Burden and predictors. J Infect. 2019 Feb. 78 (2):127-133. [QxMD MEDLINE Link].
Duchin JS, Koster FT, Peters CJ, Simpson GL, Tempest B, Zaki SR, et al. Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group. N Engl J Med. 1994 Apr 7. 330(14):949-55. [QxMD MEDLINE Link].
Levy H, Simpson SQ. Hantavirus pulmonary syndrome. Am J Respir Crit Care Med. 1994 Jun. 149(6):1710-3. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Hantavirus Pulmonary Syndrome (HPS) Cases, by State. Available at http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/epislides/episls.htm. Accessed: August 24, 2010.
World Health Organization. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO. Available at http://www.who.int/influenza/human_animal_interface/H5N1_cumulative_table_archives/en/. Accessed: August 8, 2014.
Poon LL, Guan Y, Nicholls JM, Yuen KY, Peiris JS. The aetiology, origins, and diagnosis of severe acute respiratory syndrome. Lancet Infect Dis. 2004 Nov. 4(11):663-71. [QxMD MEDLINE Link].
Beutel G, Wiesner O, Eder M, et al. Virus-associated hemophagocytic syndrome as a major contributor to death in patients with 2009 influenza A (H1N1) infection. Crit Care. 2011 Mar 2. 15(2):R80. [QxMD MEDLINE Link].
Abughali N, Khiyami A, Birnkrant DJ, Kumar ML. Severe respiratory syncytial virus pneumonia associated with primary Epstein-Barr virus infection. Pediatr Pulmonol. 2002 May. 33(5):395-8. [QxMD MEDLINE Link].
Johnstone J, Majumdar SR, Fox JD, Marrie TJ. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008 Dec. 134(6):1141-8. [QxMD MEDLINE Link].
Whitney CG, Harper SA. Lower respiratory tract infections: prevention using vaccines. Infect Dis Clin North Am. 2004 Dec. 18(4):899-917. [QxMD MEDLINE Link].
Singh AM, Moore PE, Gern JE, Lemanske RF Jr, Hartert TV. Bronchiolitis to asthma: a review and call for studies of gene-virus interactions in asthma causation. Am J Respir Crit Care Med. 2007 Jan 15. 175(2):108-19. [QxMD MEDLINE Link].
Hilleman MR. Epidemiology of adenovirus respiratory infections in military recruit populations. Ann N Y Acad Sci. 1957 Apr 19. 67(8):262-72. [QxMD MEDLINE Link].
Anderson DJ, Jordan MC. Viral pneumonia in recipients of solid organ transplants. Semin Respir Infect. 1990 Mar. 5(1):38-49. [QxMD MEDLINE Link].
Harrington RD, Hooton TM, Hackman RC, Storch GA, Osborne B, Gleaves CA, et al. An outbreak of respiratory syncytial virus in a bone marrow transplant center. J Infect Dis. 1992 Jun. 165(6):987-93. [QxMD MEDLINE Link].
Kotloff RM, Ahya VN, Crawford SW. Pulmonary complications of solid organ and hematopoietic stem cell transplantation. Am J Respir Crit Care Med. 2004 Jul 1. 170(1):22-48. [QxMD MEDLINE Link].
Barton TD, Blumberg EA. Viral pneumonias other than cytomegalovirus in transplant recipients. Clin Chest Med. 2005 Dec. 26(4):707-20, viii. [QxMD MEDLINE Link].
Meyers JD, Flournoy N, Thomas ED. Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years' experience. Rev Infect Dis. 1982 Nov-Dec. 4(6):1119-32. [QxMD MEDLINE Link].
Maravi-Poma E, Martin-Loeches I, Regidor E, et al. Severe 2009 A/H1N1v influenza in pregnant women in Spain. Crit Care Med. 2011 May. 39(5):945-951. [QxMD MEDLINE Link].
Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, Hernandez M, et al. Severe respiratory disease concurrent with the circulation of H1N1 influenza. N Engl J Med. 2009 Aug 13. 361(7):674-9. [QxMD MEDLINE Link].
Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, et al. Influenza-associated hospitalizations in the United States. JAMA. 2004 Sep 15. 292(11):1333-40. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Intensive-care patients with severe novel influenza A (H1N1) virus infection - Michigan, June 2009. MMWR Morb Mortal Wkly Rep. 2009 Jul 17. 58(27):749-52. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Updated CDC Estimates of 2009 H1N1 Influenza Cases, Hospitalizations and Deaths in the United States, April 2009 - April 10, 2010. Available at http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm. Accessed: August 8, 2014.
World Health Organization. Pandemic (H1N1) 2009 - update 89. Available at http://www.who.int/csr/don/2010_02_26/en/index.html. Accessed: August 8, 2014.
Falsey AR, Walsh EE. Respiratory syncytial virus infection in adults. Clin Microbiol Rev. 2000 Jul. 13(3):371-84. [QxMD MEDLINE Link]. [Full Text].
Pelletier G, Dery P, Abed Y, Boivin G. Respiratory tract reinfections by the new human Metapneumovirus in an immunocompromised child. Emerg Infect Dis. 2002 Sep. 8(9):976-8. [QxMD MEDLINE Link]. [Full Text].
Englund JA, Boeckh M, Kuypers J, Nichols WG, Hackman RC, Morrow RA, et al. Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients. Ann Intern Med. 2006 Mar 7. 144(5):344-9. [QxMD MEDLINE Link].
Tu CC, Chen LK, Lee YS, Ko CF, Chen CM, Yang HH, et al. An outbreak of human metapneumovirus infection in hospitalized psychiatric adult patients in Taiwan. Scand J Infect Dis. 2009. 41(5):363-7. [QxMD MEDLINE Link].
Engelhardt SJ, Halsey NA, Eddins DL, Hinman AR. Measles mortality in the United States 1971-1975. Am J Public Health. 1980 Nov. 70(11):1166-9. [QxMD MEDLINE Link]. [Full Text].
Centers for Disease Control and Prevention. Measles Cases and Outbreaks. Available at http://www.cdc.gov/measles/cases-outbreaks.html. Accessed: August 9, 2014.
US Centers for Disease Control and Prevention. Epidemiologic notes and reports: measles in HIV-infected children, United States. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00000002.htm. Accessed: October 19, 2010.
Ison MG, Fishman JA. Cytomegalovirus pneumonia in transplant recipients. Clin Chest Med. 2005 Dec. 26(4):691-705, viii. [QxMD MEDLINE Link].
Ramsey PG, Fife KH, Hackman RC, Meyers JD, Corey L. Herpes simplex virus pneumonia: clinical, virologic, and pathologic features in 20 patients. Ann Intern Med. 1982 Dec. 97(6):813-20. [QxMD MEDLINE Link].
Kallen AJ, Brunkard J, Moore Z, Budge P, Arnold KE, Fosheim G, et al. Staphylococcus aureus community-acquired pneumonia during the 2006 to 2007 influenza season. Ann Emerg Med. 2009 Mar. 53(3):358-65. [QxMD MEDLINE Link].
Govaert TM, Dinant GJ, Aretz K, Knottnerus JA. The predictive value of influenza symptomatology in elderly people. Fam Pract. 1998 Feb. 15(1):16-22. [QxMD MEDLINE Link].
Uyeki TM. Human infection with highly pathogenic avian influenza A (H5N1) virus: review of clinical issues. Clin Infect Dis. 2009 Jul 15. 49(2):279-90. [QxMD MEDLINE Link].
Dowell SF, Anderson LJ, Gary HE Jr, Erdman DD, Plouffe JF, File TM Jr, et al. Respiratory syncytial virus is an important cause of community-acquired lower respiratory infection among hospitalized adults. J Infect Dis. 1996 Sep. 174(3):456-62. [QxMD MEDLINE Link].
Weber DM, Pellecchia JM. Varicella Pneumonia: Study of Prevalence in Adult Men. JAMA. 1965 May 10. 192:572-3. [QxMD MEDLINE Link].
Ko FW, Ip M, Chan PK, Ng SS, Chau SS, Hui DS. A one-year prospective study of infectious etiology in patients hospitalized with acute exacerbations of COPD and concomitant pneumonia. Respir Med. 2008 Aug. 102(8):1109-16. [QxMD MEDLINE Link].
Bonzel L, Tenenbaum T, Schroten H, Schildgen O, Schweitzer-Krantz S, Adams O. Frequent detection of viral coinfection in children hospitalized with acute respiratory tract infection using a real-time polymerase chain reaction. Pediatr Infect Dis J. 2008 Jul. 27(7):589-94. [QxMD MEDLINE Link].
Falsey AR, McCann RM, Hall WJ, Criddle MM. Evaluation of four methods for the diagnosis of respiratory syncytial virus infection in older adults. J Am Geriatr Soc. 1996 Jan. 44(1):71-3. [QxMD MEDLINE Link].
Osiowy C. Direct detection of respiratory syncytial virus, parainfluenza virus, and adenovirus in clinical respiratory specimens by a multiplex reverse transcription-PCR assay. J Clin Microbiol. 1998 Nov. 36(11):3149-54. [QxMD MEDLINE Link]. [Full Text].
Luminex Corporation. Luminex Respiratory Viral Panel. Available at http://www.luminexcorp.com/rvp/overview.html.. Accessed: August 28, 2009.
Pettila V, Webb SA, Bailey M, et al. Acute kidney injury in patients with influenza A (H1N1) 2009. Intensive Care Med. 2011 May. 37(5):763-7. [QxMD MEDLINE Link].
Nin N, Lorente JA, Soto L, et al. Acute kidney injury in critically ill patients with 2009 influenza A (H1N1) viral pneumonia: an observational study. Intensive Care Med. 2011 May. 37(5):768-74. [QxMD MEDLINE Link].
Erard V, Huang ML, Ferrenberg J, Nguy L, Stevens-Ayers TL, Hackman RC, et al. Quantitative real-time polymerase chain reaction for detection of adenovirus after T cell-replete hematopoietic cell transplantation: viral load as a marker for invasive disease. Clin Infect Dis. 2007 Oct 15. 45(8):958-65. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Acute respiratory disease associated with adenovirus serotype 14--four states, 2006-2007. MMWR Morb Mortal Wkly Rep. 2007 Nov 16. 56(45):1181-4. [QxMD MEDLINE Link].
Kapoor M, Pringle K, Kumar A, Dearth S, Liu L, Lovchik J, et al. Clinical and laboratory findings of the first imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) into the United States. Clin Infect Dis. 2014 Aug 6. [QxMD MEDLINE Link].
Barclay L. MERS-CoV: CDC Guidance for Clinical Surveillance, Management. Medscape Medical News. Sep 27 2013. Available at http://www.medscape.com/viewarticle/811800. Accessed: October 9, 2013.
Updated Information on the Epidemiology of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Guidance for the Public, Clinicians, and Public Health Authorities, 2012-2013. MMWR Morb Mortal Wkly Rep. 2013 Sep 27. 62(38):793-6. [QxMD MEDLINE Link].
Kanne JP, Godwin JD, Franquet T, Escuissato DL, Muller NL. Viral pneumonia after hematopoietic stem cell transplantation: high-resolution CT findings. J Thorac Imaging. 2007 Aug. 22(3):292-9. [QxMD MEDLINE Link].
Peters CJ, Khan AS. Hantavirus pulmonary syndrome: the new American hemorrhagic fever. Clin Infect Dis. 2002 May 1. 34(9):1224-31. [QxMD MEDLINE Link].
Fathima P, Blyth CC, Lehmann D, Lim FJ, Abdalla T, de Klerk N, et al. The impact of pneumococcal vaccination on bacterial and viral pneumonia in Western Australian children: record linkage cohort study of 469,589 births (1996-2012). Clin Infect Dis. 2017 Oct 23. [QxMD MEDLINE Link].
Hayden FG, Osterhaus AD, Treanor JJ, Fleming DM, Aoki FY, Nicholson KG, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. GG167 Influenza Study Group. N Engl J Med. 1997 Sep 25. 337(13):874-80. [QxMD MEDLINE Link].
Hayden FG, Treanor JJ, Fritz RS, Lobo M, Betts RF, Miller M, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA. 1999 Oct 6. 282(13):1240-6. [QxMD MEDLINE Link].
Hayden FG, Atmar RL, Schilling M, Johnson C, Poretz D, Paar D, et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med. 1999 Oct 28. 341(18):1336-43. [QxMD MEDLINE Link].
Hirji Z, O'Grady S, Bonham J, Mak M, Takata-Shewchuk J, Hawkins K, et al. Utility of zanamivir for chemoprophylaxis of concomitant influenza A and B in a complex continuing-care population. Can Commun Dis Rep. 2001 Feb 1. 27(3):21-4. [QxMD MEDLINE Link].
Monto AS, Fleming DM, Henry D, de Groot R, Makela M, Klein T, et al. Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections. J Infect Dis. 1999 Aug. 180(2):254-61. [QxMD MEDLINE Link].
Treanor JJ, Hayden FG, Vrooman PS, Barbarash R, Bettis R, Riff D, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA. 2000 Feb 23. 283(8):1016-24. [QxMD MEDLINE Link].
Kohno S, Kida H, Mizuguchi M, Shimada J. Efficacy and safety of intravenous peramivir for treatment of seasonal influenza virus infection. Antimicrob Agents Chemother. 2010 Nov. 54(11):4568-74. [QxMD MEDLINE Link]. [Full Text].
Watanabe A, Chang SC, Kim MJ, Chu DW, Ohashi Y. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza: A double-blind, randomized, noninferiority clinical trial. Clin Infect Dis. 2010 Nov 15. 51(10):1167-75. [QxMD MEDLINE Link].
Martin-Loeches I, Lisboa T, Rhodes A, Moreno RP, Silva E, Sprung C, et al. Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1)v influenza A infection. Intensive Care Med. 2011 Feb. 37(2):272-83. [QxMD MEDLINE Link].
Moscona A. Management of respiratory syncytial virus infections in the immunocompromised child. Pediatr Infect Dis J. 2000 Mar. 19(3):253-4. [QxMD MEDLINE Link].
Swedish Consensus Group. Management of infections caused by respiratory syncytial virus. Scand J Infect Dis. 2001. 33(5):323-8. [QxMD MEDLINE Link].
Bordigoni P, Carret AS, Venard V, Witz F, Le Faou A. Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2001 May 1. 32(9):1290-7. [QxMD MEDLINE Link].
Morfin F, Dupuis-Girod S, Frobert E, Mundweiler S, Carrington D, Sedlacek P, et al. Differential susceptibility of adenovirus clinical isolates to cidofovir and ribavirin is not related to species alone. Antivir Ther. 2009. 14(1):55-61. [QxMD MEDLINE Link].
Kapelushnik J, Or R, Delukina M, Nagler A, Livni N, Engelhard D. Intravenous ribavirin therapy for adenovirus gastroenteritis after bone marrow transplantation. J Pediatr Gastroenterol Nutr. 1995 Jul. 21(1):110-2. [QxMD MEDLINE Link].
McCarthy AJ, Bergin M, De Silva LM, Stevens M. Intravenous ribavirin therapy for disseminated adenovirus infection. Pediatr Infect Dis J. 1995 Nov. 14(11):1003-4. [QxMD MEDLINE Link].
Adenovirus. Am J Transplant. 2004 Nov. 4 Suppl 10:101-4. [QxMD MEDLINE Link].
Chakrabarti S, Collingham KE, Holder K, Fegan CD, Osman H, Milligan DW. Pre-emptive oral ribavirin therapy of paramyxovirus infections after haematopoietic stem cell transplantation: a pilot study. Bone Marrow Transplant. 2001 Oct. 28(8):759-63. [QxMD MEDLINE Link].
Safdar A. Immune modulatory activity of ribavirin for serious human metapneumovirus disease: early i.v. therapy may improve outcomes in immunosuppressed SCT recipients. Bone Marrow Transplant. 2008 Apr. 41(8):707-8. [QxMD MEDLINE Link].
Raza K, Ismailjee SB, Crespo M, Studer SM, Sanghavi S, Paterson DL, et al. Successful outcome of human metapneumovirus (hMPV) pneumonia in a lung transplant recipient treated with intravenous ribavirin. J Heart Lung Transplant. 2007 Aug. 26(8):862-4. [QxMD MEDLINE Link].
Bonney D, Razali H, Turner A, Will A. Successful treatment of human metapneumovirus pneumonia using combination therapy with intravenous ribavirin and immune globulin. Br J Haematol. 2009 Jun. 145(5):667-9. [QxMD MEDLINE Link].
Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. 2004 Mar. 59(3):252-6. [QxMD MEDLINE Link]. [Full Text].
Chen F, Chan KH, Jiang Y, Kao RY, Lu HT, Fan KW, et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol. 2004 Sep. 31(1):69-75. [QxMD MEDLINE Link].
Forni AL, Schluger NW, Roberts RB. Severe measles pneumonitis in adults: evaluation of clinical characteristics and therapy with intravenous ribavirin. Clin Infect Dis. 1994 Sep. 19(3):454-62. [QxMD MEDLINE Link].
Petarra-Del Río S, Rodriguez-Hernandez A, Anguiano-Landa L, Aguilar-Portillo G, Zavala-Trujillo I, Nava-Zavala AH, et al. Immune Reconstitution Inflammatory Syndrome and Cytomegalovirus Pneumonia Case Report: Highlights and Missing Links in Classification Criteria and Standardized Treatment. Case Rep Infect Dis. 2017. 2017:9314580. [QxMD MEDLINE Link].
Zamora MR. Cytomegalovirus and lung transplantation. Am J Transplant. 2004 Aug. 4(8):1219-26. [QxMD MEDLINE Link].
Bacigalupo A, Bregante S, Tedone E, Isaza A, Van Lint MT, Moro F, et al. Combined foscarnet -ganciclovir treatment for cytomegalovirus infections after allogeneic hemopoietic stem cell transplantation (Hsct). Bone Marrow Transplant. 1996 Nov. 18 Suppl 2:110-4. [QxMD MEDLINE Link].
Centers for Disease Control and Prevention. Seasonal Influenza (Flu). Recommendations of the Advisory Committee on Immunization Practices (ACIP). Available at http://www.cdc.gov/flu/professionals/acip/. Accessed: August 8, 2014.
van der Hoek L. Human coronaviruses: what do they cause?. Antivir Ther. 2007. 12(4 Pt B):651-8. [QxMD MEDLINE Link].
Huijts SM, Coenjaerts FEJ, Bolkenbaas M, van Werkhoven CH, Grobbee DE, Bonten MJM, et al. The impact of 13-valent pneumococcal conjugate vaccination on virus-associated community-acquired pneumonia in elderly: Exploratory analysis of the CAPiTA trial. Clin Microbiol Infect. 2017 Oct 16. [QxMD MEDLINE Link].
Tang RS, Schickli JH, MacPhail M, et al. Effects of human metapneumovirus and respiratory syncytial virus antigen insertion in two 3' proximal genome positions of bovine/human parainfluenza virus type 3 on virus replication and immunogenicity. J Virol. 2003 Oct. 77(20):10819-28. [QxMD MEDLINE Link]. [Full Text].
Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009 Oct. 15(10):1143-238. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Pneumonia, viral: A 52-year-old woman developed fever, cough, and dyspnea. She also developed a rash that was prominent over the face and the trunk. The chest radiograph showed interstitial infiltrates, with suggestion of a micronodular process. The Tzanck smear results from the skin vesicle suggest varicella-zoster virus.
Pneumonia, viral: A 52-year-old woman developed fever, cough, and dyspnea. She also developed a rash that was prominent over the face and the trunk. The chest radiograph showed interstitial infiltrates, with suggestion of a micronodular process. The Tzanck smear results from the skin vesicle suggest varicella-zoster virus. She was treated with acyclovir; resolution of varicella-zoster virus infection occurred after 7 days of therapy.
Bilateral interstitial infiltrates in a 31-year-old patient with influenza pneumonia.
Right-middle-lobe infiltrate in a 2-month-old boy with pneumonia due to respiratory syncytial virus (RSV).
High-power Papanicolaou (Pap) stain showing a virus on a bronchial wash. Viruses in general show "smudgy" nuclei, may or may not show nuclear or cytoplasmic inclusions, and may demonstrate other features such as multinucleation or margination of chromatin to the periphery of the cell nucleus. Certain features are more indicative of one virus over another. This is an example of herpes virus (cells infected are located in the center right).
High-power Papanicolaou (Pap) stain of cytomegalovirus (center). This cell has a very large, dark intranuclear inclusion.
High-power hematoxin-and-eosin stain of giant cell pneumonia following measles. A multinucleated cell (center) contains eosinophilic intranuclear inclusions.
High-power hematoxin-and-eosin stain of numerous cells infected with the cytomegalovirus (large cells with enlarged nuclei containing dark-purple intranuclear inclusions surrounded by a clear halo).
High-power hematoxin-and-eosin stained herpes simplexvirus, characterized by "smudgy" degenerating nuclei. Some cells are multinucleated with margination of the chromatin to the periphery of the nuclei and molding of the nuclei to each other.

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Table 1. Diagnostic Techniques Used for Viral Pneumonia

Virus	Viral Culture	Cytologic Evaluation	Rapid Antigen Detection	Gene Amplification
Influenza virus	HA^a, SV^b		IF^c, ELISA^d	RT-PCR^e
Adenovirus	CE^f, SV	Intranuclear inclusions	IF, ELISA	RT-PCR
Paramyxoviruses
Respiratory syncytial virus	CE, SV	Eosinophilic cytoplasmic inclusions	IF, ELISA	RT-PCR
Parainfluenza virus	HA, SV	Eosinophilic intranuclear inclusions	IF, ELISA	RT-PCR
Measles virus	HA
Herpes viruses
Herpes simplex virus	CE, SV	Cytoplasmic inclusions	IF, ELISA	PCR
Varicella-zoster virus	CE	Cytoplasmic inclusions	IF	RT-PCR
Cytomegalovirus	CE, SV	"Owl's eye" cells	IF, ELISA	RT-PCR
Hantavirus			Antibodies against FCV^g	FVC RNA by RT-PCR
^a HA - Hemaglutination ^b SV - Shell viral culture ^c IF - Immunofluorescence ^d ELISA - Enzyme-linked immunosorbent assay ^eRT-PCR - Reverse transcriptase polymerase chain reaction ^fCE - Cytopathogenic effects ^gFCV - Four corners virus

Table 2. Treatment and Prevention of Common Causes of Viral Pneumonia

Virus	Treatment	Prevention
Influenza virus	Oseltamivir Peramivir Zanamivir	Influenza vaccine^[77] Chemoprophylaxis with: Zanamivir Oseltamivir
Respiratory syncytial virus	Ribavirin	RSV immunoglobulin Palivizumab
Parainfluenza virus	Ribavirin
Herpes simplex virus	Acyclovir
Varicella-zoster virus	Acyclovir	Varicella-zoster immunoglobulin
Adenovirus	Ribavirin
Measles virus	Ribavirin	Intravenous immunoglobulin
Cytomegalovirus	Ganciclovir Foscarnet	Intravenous immunoglobulin

Table 3. Characteristics of Anti-Influenza Drugs

	Amantadine (Symmetrel)	Rimantadine (Flumadine)	Zanamivir (Relenza)	Oseltamivir (Tamiflu)
Mechanism of action	M2 ion channel blockade inhibits HA^a cleavage beta block RNA encoding, which reduces early viral replication.		Viral NA^b inhibition prevents sialic acid cleavage from HA beta virus gets trapped inside cells, and epithelial spread is blocked.
Spectrum	Influenza A only	Influenza A only	Influenza A and B	Influenza A and B
Oral bioavailability	Good	Good	Poor	Good
Protein binding, %	67	40	None	Minimal
Half-life, h	12-18	24-36	2.5-5	1-3
Excretion	Renal (not removed by hemodialysis)		Renal and gastrointestinal	Renal
Drug interaction	Synergistic CNS toxicity with antihistamines, anticholinergics, CNS stimulants	Beta Plasma level: ASA^c, acetaminophen	None	None
Renal clearance	TMP-SMZ^d, triamterene, hydrochlorothiazide, quinine sulfate, quinidine	Cimetidine	None	None
^a HA - Hemagglutinin ^b NA - Neuraminidase ^c ASA - Acetylsalicylic acid ^d TMP-SMZ - Trimethoprim and sulfamethoxazole

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Author

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Arthur Jeng, MD Assistant Professor of Clinical Medicine, University of California at Los Angeles School of Medicine

Arthur Jeng, MD is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Nader Kamangar, MD, FACP, FCCP, FCCM Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Medicine, Olive View-UCLA Medical Center

Nader Kamangar, MD, FACP, FCCP, FCCM is a member of the following medical societies: Academy of Persian Physicians, American Academy of Sleep Medicine, American Association for Bronchology and Interventional Pulmonology, American College of Chest Physicians, American College of Critical Care Medicine, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, Association of Pulmonary and Critical Care Medicine Program Directors, Association of Specialty Professors, California Sleep Society, California Thoracic Society, Clerkship Directors in Internal Medicine, Society of Critical Care Medicine, Trudeau Society of Los Angeles, World Association for Bronchology and Interventional Pulmonology

Disclosure: Nothing to disclose.

Chief Editor

John J Oppenheimer, MD Clinical Professor, Department of Medicine, Rutgers New Jersey Medical School; Director of Clinical Research, Pulmonary and Allergy Associates, PA

John J Oppenheimer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, New Jersey Allergy, Asthma and Immunology Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Amgen; GSK; Aquestive; Aimmune<br/>Clinical Adjudication/Data Safety Monitoring Board for AZ, GSK, Abbvie, Sanofi; Executive Editor for Annals of Allergy, Asthma & Immunology; Editor for Medscape; Reviewer for UpToDate; Honoraria from American Board of Allergy and Immunology.

Acknowledgements

Shakeel Amanullah, MD Consulting Physician, Pulmonary, Critical Care, and Sleep Medicine, Lancaster General Hospital

Shakeel Amanullah, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine