The Clinical Presentation and Immunology of Viral Pneumonia and Implications for Management of Coronavirus Disease 2019

Dijoia B Darden, Russell B Hawkins, Shawn D Larson, Nicole M Iovine, Donald S Prough, Philip A Efron, Dijoia B Darden, Russell B Hawkins, Shawn D Larson, Nicole M Iovine, Donald S Prough, Philip A Efron

Abstract

This review will briefly examine the clinical presentation and important immunology of viral pneumonia with a focus on severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019).

Data sources study selection data extraction and data synthesis: The most relevant, original and review literature were assessed for inclusion in this review. Sources included the Centers for Disease Control and Prevention, World Health Organization, and PubMed.

Conclusions: Pneumonia is a leading cause of hospitalization and death worldwide, with viral etiologies being very common. Given the rapidly emerging pandemic associated with the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019, it is important to review the clinical presentation and immunologic changes associated with viral pneumonia. Symptoms of viral pneumonia include common respiratory tract infection symptoms of cough, fever, and shortness of breath. Immunologic changes include up-regulation of airway pro-inflammatory cytokines and pathogen- and damage-associated molecular patterns contributing to cytokine and genomic changes. Coronavirus disease 2019 clinical presentation is typical of viral pneumonia with an increased prevalence of early pulmonary infiltrates and lymphopenia. Principles of early coronavirus disease 2019 management and isolation as well as potential therapeutic approaches to the emerging pandemic are discussed.

Keywords: coronavirus; immunology; influenza virus; severe acute respiratory syndrome; viral pneumonia.

Conflict of interest statement

The authors have disclosed that they do not have any potential conflicts of interest.

Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.

References

    1. Pfuntner A, Wier LM, Stocks C. Most Frequent Conditions in U.S. Hospitals, 2011: Statistical Brief #162. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. 2006, Rockville, MD: Agency for Healthcare Research and Quality (US) Available at: . Accessed March 27, 2020
    1. World Health Organization: The Top 10 Causes of Death. 2018. Available at: . Accessed March 23, 2020
    1. Jain S, Self WH, Wunderink RG, et al. ; CDC EPIC Study Team. Community-acquired pneumonia requiring hospitalization among U.S. adults. N Engl J Med. 2015; 373:415–427
    1. Jain S. Epidemiology of viral pneumonia. Clin Chest Med. 2017; 38:1–9
    1. Shorr AF, Zilberberg MD, Micek ST, et al. Viruses are prevalent in non-ventilated hospital-acquired pneumonia. Respir Med. 2017; 122:76–80
    1. Alimi Y, Lim WS, Lansbury L, et al. Systematic review of respiratory viral pathogens identified in adults with community-acquired pneumonia in Europe. J Clin Virol. 2017; 95:26–35
    1. Burk M, El-Kersh K, Saad M, et al. Viral infection in community-acquired pneumonia: A systematic review and meta-analysis. Eur Respir Rev. 2016; 25:178–188
    1. Choi SH, Huh JW, Hong SB, et al. Clinical characteristics and outcomes of severe rhinovirus-associated pneumonia identified by bronchoscopic bronchoalveolar lavage in adults: Comparison with severe influenza virus-associated pneumonia. J Clin Virol. 2015; 62:41–47
    1. Johnstone J, Majumdar SR, Fox JD, et al. Viral infection in adults hospitalized with community-acquired pneumonia: Prevalence, pathogens, and presentation. Chest. 2008; 134:1141–1148
    1. Moore M, Stuart B, Little P, et al. Predictors of pneumonia in lower respiratory tract infections: 3C prospective cough complication cohort study. Eur Respir J. 2017; 50:1700434.
    1. Shorr AF, Fisher K, Micek ST, et al. The burden of viruses in pneumonia associated with acute respiratory failure: An underappreciated issue. Chest. 2018; 154:84–90
    1. Dunham-Snary KJ, Wu D, Sykes EA, et al. Hypoxic pulmonary vasoconstriction: From molecular mechanisms to medicine. Chest. 2017; 151:181–192
    1. Paules C, Subbarao K. Influenza. Lancet. 2017; 390:697–708
    1. Kalil AC, Thomas PG. Influenza virus-related critical illness: Pathophysiology and epidemiology. Crit Care. 2019; 23:258.
    1. Yeldandi AV, Colby TV. Pathologic features of lung biopsy specimens from influenza pneumonia cases. Hum Pathol. 1994; 25:47–53
    1. Guarner J, Shieh WJ, Dawson J, et al. Immunohistochemical and in situ hybridization studies of influenza A virus infection in human lungs. Am J Clin Pathol. 2000; 114:227–233
    1. Martin CM, Kunin CM, Gottlieb LS, et al. Asian influenza A in Boston, 1957-1958. I. Observations in thirty-two influenza-associated fatal cases. AMA Arch Intern Med. 1959; 103:515–531
    1. Percopo CM, Dyer KD, Ochkur SI, et al. Activated mouse eosinophils protect against lethal respiratory virus infection. Blood. 2014; 123:743–752
    1. Hermesh T, Moltedo B, Moran TM, et al. Antiviral instruction of bone marrow leukocytes during respiratory viral infections. Cell Host Microbe. 2010; 7:343–353
    1. Davey RT, Jr, Lynfield R, Dwyer DE, et al. ; INSIGHT FLU 002 & 003 Study Groups. The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: Results of two international observational cohort studies. PLoS One. 2013; 8:e57121.
    1. Rodriguez-Ramirez HG, Salinas-Carmona MC, Barboza-Quintana O, et al. CD206+ cell number differentiates influenza A (H1N1)pdm09 from seasonal influenza A virus in fatal cases. Mediators Inflamm. 2014; 2014:921054.
    1. Zobel K, Martus P, Pletz MW, et al. ; CAPNETZ study group. Interleukin 6, lipopolysaccharide-binding protein and interleukin 10 in the prediction of risk and etiologic patterns in patients with community-acquired pneumonia: Results from the German competence network CAPNETZ. BMC Pulm Med. 2012; 12:6.
    1. Endeman H, Meijvis SC, Rijkers GT, et al. Systemic cytokine response in patients with community-acquired pneumonia. Eur Respir J. 2011; 37:1431–1438
    1. Burgmeijer EH, Duijkers R, Lutter R, et al. Plasma cytokine profile on admission related to aetiology in community-acquired pneumonia. Clin Respir J. 2019; 13:605–613
    1. Siljan WW, Holter JC, Nymo SH, et al. Cytokine responses, microbial aetiology and short-term outcome in community-acquired pneumonia. Eur J Clin Invest. 2018; 48:e12865
    1. Rendon A, Rendon-Ramirez EJ, Rosas-Taraco AG. Relevant cytokines in the management of community-acquired pneumonia. Curr Infect Dis Rep. 2016; 18:10.
    1. Rendón-Ramirez EJ, Ortiz-Stern A, Martinez-Mejia C, et al. TGF-β blood levels distinguish between influenza a (H1N1)pdm09 virus sepsis and sepsis due to other forms of community-acquired pneumonia. Viral Immunol. 2015; 28:248–254
    1. Paats MS, Bergen IM, Hanselaar WE, et al. Local and systemic cytokine profiles in nonsevere and severe community-acquired pneumonia. Eur Respir J. 2013; 41:1378–1385
    1. Kellum JA, Kong L, Fink MP, et al. ; GenIMS Investigators. Understanding the inflammatory cytokine response in pneumonia and sepsis: Results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007; 167:1655–1663
    1. Donnelly SC, Strieter RM, Reid PT, et al. The association between mortality rates and decreased concentrations of interleukin-10 and interleukin-1 receptor antagonist in the lung fluids of patients with the adult respiratory distress syndrome. Ann Intern Med. 1996; 125:191–196
    1. Takeuchi O, Akira S. Innate immunity to virus infection. Immunol Rev. 2009; 227:75–86
    1. Creagh EM, O’Neill LA. TLRs, NLRs and RLRs: A trinity of pathogen sensors that co-operate in innate immunity. Trends Immunol. 2006; 27:352–357
    1. Wilkins C, Gale M., Jr Recognition of viruses by cytoplasmic sensors. Curr Opin Immunol. 2010; 22:41–47
    1. Yoo JK, Kim TS, Hufford MM, et al. Viral infection of the lung: Host response and sequelae. J Allergy Clin Immunol. 2013; 132:1263–1276; quiz 1277
    1. Pang IK, Iwasaki A. Inflammasomes as mediators of immunity against influenza virus. Trends Immunol. 2011; 32:34–41
    1. Shi Y, Evans JE, Rock KL. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 2003; 425:516–521
    1. Ichinohe T, Pang IK, Iwasaki A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol. 2010; 11:404–410
    1. Muruve DA, Pétrilli V, Zaiss AK, et al. The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature. 2008; 452:103–107
    1. Koyama S, Ishii KJ, Kumar H, et al. Differential role of TLR- and RLR-signaling in the immune responses to influenza A virus infection and vaccination. J Immunol. 2007; 179:4711–4720
    1. Heer AK, Shamshiev A, Donda A, et al. TLR signaling fine-tunes anti-influenza B cell responses without regulating effector T cell responses. J Immunol. 2007; 178:2182–2191
    1. Jennings LC, Anderson TP, Beynon KA, et al. Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax. 2008; 63:42–48
    1. Abelenda-Alonso G, Rombauts A, Gudiol C, et al. Influenza and bacterial coinfection in adults with community-acquired pneumonia admitted to conventional wards: Risk factors, clinical features, and outcomes. Open Forum Infect Dis. 2020; 7:ofaa066.
    1. Cawcutt K, Kalil AC. Pneumonia with bacterial and viral coinfection. Curr Opin Crit Care. 2017; 23:385–390
    1. Talbot TR, Poehling KA, Hartert TV, et al. Seasonality of invasive pneumococcal disease: Temporal relation to documented influenza and respiratory syncytial viral circulation. Am J Med. 2005; 118:285–291
    1. Robinson KM, Kolls JK, Alcorn JF. The immunology of influenza virus-associated bacterial pneumonia. Curr Opin Immunol. 2015; 34:59–67
    1. van der Sluijs KF, van der Poll T, Lutter R, et al. Bench-to-bedside review: Bacterial pneumonia with influenza - pathogenesis and clinical implications. Crit Care. 2010; 14:219.
    1. Damjanovic D, Lai R, Jeyanathan M, et al. Marked improvement of severe lung immunopathology by influenza-associated pneumococcal superinfection requires the control of both bacterial replication and host immune responses. Am J Pathol. 2013; 183:868–880
    1. Ghoneim HE, Thomas PG, McCullers JA. Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections. J Immunol. 2013; 191:1250–1259
    1. Kudva A, Scheller EV, Robinson KM, et al. Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice. J Immunol. 2011; 186:1666–1674
    1. Pittet LA, Hall-Stoodley L, Rutkowski MR, et al. Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae. Am J Respir Cell Mol Biol. 2010; 42:450–460
    1. Plotkowski MC, Puchelle E, Beck G, et al. Adherence of type I Streptococcus pneumoniae to tracheal epithelium of mice infected with influenza A/PR8 virus. Am Rev Respir Dis. 1986; 134:1040–1044
    1. Tanaka A, Nakamura S, Seki M, et al. Toll-like receptor 4 agonistic antibody promotes innate immunity against severe pneumonia induced by coinfection with influenza virus and Streptococcus pneumoniae. Clin Vaccine Immunol. 2013; 20:977–985
    1. Didierlaurent A, Goulding J, Patel S, et al. Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection. J Exp Med. 2008; 205:323–329
    1. Waterer GW. Community-acquired pneumonia: Genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Semin Respir Crit Care Med. 2012; 33:257–265
    1. Bermejo-Martin JF, Martin-Loeches I, Rello J, et al. Host adaptive immunity deficiency in severe pandemic influenza. Crit Care. 2010; 14:R167.
    1. Kim H, Webster RG, Webby RJ. Influenza virus: Dealing with a drifting and shifting pathogen. Viral Immunol. 2018; 31:174–183
    1. Mei L, Song P, Tang Q, et al. Changes in and shortcomings of control strategies, drug stockpiles, and vaccine development during outbreaks of avian influenza A H5N1, H1N1, and H7N9 among humans. Biosci Trends. 2013; 7:64–76
    1. Gao R, Cao B, Hu Y, et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med. 2013; 368:1888–1897
    1. Bautista E, Chotpitayasunondh T, Gao Z, et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med. 2010; 362:1708–1719
    1. Cox NJ, Subbarao K. Global epidemiology of influenza: Past and present. Annu Rev Med. 2000; 51:407–421
    1. Jackson ML, Chung JR, Jackson LA, et al. Influenza vaccine effectiveness in the United States during the 2015-2016 season. N Engl J Med. 2017; 377:534–543
    1. Desmet CJ, Ishii KJ. Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol. 2012; 12:479–491
    1. Hayashi T, Momota M, Kuroda E, et al. DAMP-inducing adjuvant and PAMP adjuvants parallelly enhance protective type-2 and type-1 immune responses to influenza split vaccination. Front Immunol. 2018; 9:2619.
    1. Ruuskanen O, Lahti E, Jennings LC, et al. Viral pneumonia. Lancet. 2011; 377:1264–1275
    1. O’Donnell FL, Taubman SB. Follow-up analysis of the incidence of acute respiratory infections among enlisted service members during their first year of military service before and after the 2011 resumption of adenovirus vaccination of basic trainees. MSMR. 2015; 22:2–7
    1. Radin JM, Hawksworth AW, Blair PJ, et al. Dramatic decline of respiratory illness among US military recruits after the renewed use of adenovirus vaccines. Clin Infect Dis. 2014; 59:962–968
    1. Clemmons NS, McCormic ZD, Gaydos JC, et al. Acute respiratory disease in US army trainees 3 years after reintroduction of adenovirus vaccine (1). Emerg Infect Dis. 2017; 23:95–98
    1. Tucker SN, Tingley DW, Scallan CD. Oral adenoviral-based vaccines: Historical perspective and future opportunity. Expert Rev Vaccines. 2008; 7:25–31
    1. Joyce C, Scallan CD, Mateo R, et al. Orally administered adenoviral-based vaccine induces respiratory mucosal memory and protection against RSV infection in cotton rats. Vaccine. 2018; 36:4265–4277
    1. Scheltema NM, Nibbelke EE, Pouw J, et al. Respiratory syncytial virus prevention and asthma in healthy preterm infants: A randomised controlled trial. Lancet Respir Med. 2018; 6:257–264
    1. Blanken MO, Rovers MM, Bont L; Dutch RSV Neonatal Network. Respiratory syncytial virus and recurrent wheeze. N Engl J Med. 2013; 369:782–783
    1. Fainaru M, Schafer Z, Gavish D, et al. Interactions between human and carp (Cyprimus carpio) low density lipoproteins (LDL) and LDL receptors. Comp Biochem Physiol B. 1988; 91:331–338
    1. Driscoll AJ, Arshad SH, Bont L, et al. Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting. Vaccine. 2020; 38:2435–2448
    1. Del Rio C, Malani PN. COVID-19-new insights on a rapidly changing epidemic. JAMA. 2020. Feb 28. [online ahead of print]
    1. Guan WJ, Ni ZY, Hu Y, et al. ; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020. Feb 28. [online ahead of print]
    1. Bermejo-Martin JF, Almansa R, Menendez R, et al. Lymphopenic community acquired pneumonia as signature of severe COVID-19 infection. J Infect. 2020. Mar 5. [online ahead of print]
    1. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med. 2020. Feb 24. [online ahead of print]
    1. Bermejo-Martin JF, Martin-Fernandez M, Lopez-Mestanza C, et al. Shared features of endothelial dysfunction between sepsis and its preceding risk factors (aging and chronic disease). J Clin Med. 2018; 7:400
    1. Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020; 38:1–9
    1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395:497–506
    1. Marchand-Senecal X, Kozak R, Mubareka S, et al. Diagnosis and management of first case of COVID-19 in Canada: Lessons applied from SARS. Clin Infect Dis. 2020. Mar 9. [online ahead of print]
    1. Chinese Clinical Trial Register: A randomized, controlled open-label trial to evaluate the efficacy and safety of lopinavir-ritonavir in hospitalized patients with novel coronavirus pneumonia (COVID-19) 2020, Chengdu, Sichuan, China: Ministry of Health (China). H. ChiCTR2000029308; Available at: . Accessed March 23, 2020
    1. Cao B, Wang Y, Wen D, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 2020. Mar 18. [online ahead of print]
    1. Fauci AS, Lane HC, Redfield RR. Covid-19 - navigating the uncharted. N Engl J Med. 2020; 382:1268–1269
    1. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020. Mar 20. [online ahead of print]
    1. Ahmed SF, Quadeer AA, McKay MR. Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies. Viruses. 2020; 12:E254.
    1. Wan Y, Shang J, Graham R, et al. Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus. J Virol. 2020; 94:e00127–20
    1. Jiang F, Deng L, Zhang L, et al. Review of the clinical characteristics of coronavirus disease 2019 (COVID-19). J Gen Intern Med. 2020. Mar 4. [online ahead of print]
    1. World Health Organization: Coronavirus Disease (COVID-19) Technical Guidance: Infection Prevention and Control/WASH. 2020. Available at: . Accessed March 23, 2020

Source: PubMed

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