Viral Respiratory Infections: an Overview

Acute respiratory infection is the most common illness of otherwise healthy people, and the great majority of it is viral. Young children experience five to nine such illnesses a year and adults two or three, most of them trivial colds and sore throats that nonetheless account for an enormous burden of lost work and school days and a large share of visits to primary care. In surveyed populations acute respiratory illness runs at over 85 episodes per 100 people a year, makes up around half of all acute conditions, and leads to medical attention in close to half of episodes. The serious disease sits at the extremes of life and in those with underlying lung or heart disease.

Respiratory infection is a leading cause of childhood death in low- and middle-income countries, where viruses contribute to a substantial fraction of the millions of deaths from acute respiratory infection in children under five each year. The two agents that matter most for severe disease are influenza, which kills mainly the old, and respiratory syncytial virus (RSV), which kills mainly the very young.

Two ideas organise the whole field. The first is the anatomical gradient. As infection descends the respiratory tract, six syndromes of increasing severity are described: rhinitis (the common cold), pharyngitis, croup, bronchitis, bronchiolitis and pneumonia. This mapping is a tendency rather than a rule. Most respiratory viruses can cause disease at any level of the tract, the same virus produces different syndromes in different hosts (even within one household), and a single syndrome can be caused by many unrelated viruses. The syndrome that results depends heavily on the age and immune status of the host.

The second idea is immunity. Viruses whose infection stays confined to the respiratory mucosa, with little or no viraemia, provoke only a transient secretory immunoglobulin A (IgA) response and a weaker systemic one, so reinfection with the same or a drifted strain recurs throughout life. This contrasts with the viruses that enter by the respiratory route but then spread through the bloodstream, such as measles and varicella-zoster virus, which generate durable immunity and produce systemic disease. The syndromes and their viral causes are the organising thread, taken together with the epidemiology, pathogenesis, natural history and complications of each; the replication and structure of the individual viruses are the province of their own agent-level accounts.

The viruses and their families

Respiratory disease is caused by both RNA and DNA viruses drawn from a handful of families. Knowing the family predicts a good deal about genome, structure and behaviour.

Family	Genome	Principal human respiratory viruses	Typical syndromes
Orthomyxoviridae	Segmented negative-sense RNA	Influenza A and B (C minor)	Influenzal illness, tracheobronchitis, pneumonia
Pneumoviridae	Negative-sense RNA	RSV, human metapneumovirus	Bronchiolitis, pneumonia, colds
Paramyxoviridae	Negative-sense RNA	Parainfluenza 1 to 4, measles, mumps	Croup, colds, pneumonia
Picornaviridae	Positive-sense RNA	Rhinoviruses, enteroviruses (including D68)	Common cold, pharyngitis, wheeze
Coronaviridae	Positive-sense RNA	Four common-cold coronaviruses; SARS-CoV, MERS-CoV, SARS-CoV-2	Colds; severe pneumonia and respiratory failure
Adenoviridae	Double-stranded DNA	Adenoviruses (many types)	Pharyngoconjunctival fever, pneumonia
Herpesviridae	Double-stranded DNA	HSV, VZV, EBV, CMV	Pharyngitis, pneumonia (mainly immunocompromised)

Two taxonomic points are worth flagging because the older literature places them differently. RSV and human metapneumovirus (hMPV) now sit in their own family, Pneumoviridae, having been moved out of the paramyxoviruses; RSV is an orthopneumovirus and hMPV a metapneumovirus.

Among the coronaviruses, seven are known to infect humans: the four endemic agents that cause common colds (229E and NL63 in the alphacoronaviruses, OC43 and HKU1 in the betacoronaviruses) and three betacoronaviruses capable of severe pneumonia, the severe acute respiratory syndrome coronavirus (SARS-CoV, 2003), the Middle East respiratory syndrome coronavirus (MERS-CoV, 2012), and SARS-CoV-2, the cause of COVID-19 and the largest respiratory pandemic in a century.

Seasonal patterns

Many respiratory viruses vary predictably in incidence, which is useful both diagnostically and for planning services. Influenza and RSV epidemics fall in the winter months, with peaks that usually stagger rather than coincide. Parainfluenza virus type 3 peaks in spring while types 1 and 2 cause autumn and early-winter outbreaks, giving croup its seasonal rhythm. Rhinoviruses circulate year-round with increases in spring and autumn, enteroviruses peak in late summer and early autumn, and adenoviruses circulate at a fairly steady rate throughout the year. Standard models of respiratory virus seasonality are largely derived from Northern Hemisphere data and may not reflect the distinct transmission dynamics of different climatic regions.

Reinfection and the age gradient

Respiratory viruses are unusual among human pathogens in reinfecting the same person repeatedly across a lifetime. For the agents confined to the mucosa the reason is immunological: the transient secretory response leaves little durable protection, so RSV, the parainfluenza viruses, the endemic coronaviruses and the rhinoviruses (of which there are more than a hundred types) are met again and again. Influenza adds a second mechanism, antigenic drift and shift, in which the surface proteins change enough that prior immunity no longer recognises the virus, producing seasonal epidemics and, occasionally, pandemics.

Age then shapes which syndrome results. Infancy brings the severe lower-tract syndromes, bronchiolitis and croup, when the small airways are most vulnerable; young children carry the highest rates of colds and of viral pneumonia; healthy adults mostly experience upper-tract illness; and the elderly, like the very young, return to severe lower-tract disease and death, chiefly from influenza and RSV. The systemic respiratory-route viruses such as measles behave differently again, provoking lifelong immunity after a single childhood infection.

Respiratory syndromes and their principal viral causes

The same look-up recurs in clinical practice: a syndrome is recognised, and the question is which viruses to expect. The grid below groups the agents by how often they cause each syndrome. It is a guide to probability, not a diagnosis: the individual agent usually cannot be told from the syndrome alone.

Syndrome	Common (over 15%)	Less common (5 to 15%)	Occasional
Rhinitis (common cold)	Rhinoviruses	RSV, hMPV, coronaviruses	Parainfluenza, influenza, adenoviruses, coxsackie and echoviruses
Pharyngitis	Adenoviruses	Rhinoviruses, influenza, parainfluenza, EBV, coxsackie A	RSV, coronaviruses, CMV, HSV
Croup (laryngotracheobronchitis)	Parainfluenza 1 and 2	RSV, influenza, coronaviruses, adenoviruses	Rhinoviruses, parainfluenza 3
Bronchitis and tracheobronchitis	Influenza	Parainfluenza 3, RSV	Parainfluenza 1 and 2, rhinoviruses, adenoviruses
Bronchiolitis	RSV	Parainfluenza 3, hMPV, adenoviruses	Influenza A, rhinoviruses, enteroviruses
Pneumonia (children under 5)	RSV, parainfluenza 3	Influenza, adenoviruses, CMV	Rhinoviruses, VZV, enterovirus D68
Pneumonia (adults)	Influenza, SARS-CoV-2	Adenoviruses	RSV, measles, coronaviruses, VZV
Pneumonia (immunocompromised)	CMV	Adenoviruses, RSV, HSV	Influenza, parainfluenza 3

The grid derives from a classification drawn up before 2019, so SARS-CoV-2 has been added to the adult-pneumonia row; it is now a leading cause of severe community pneumonia and of the acute respiratory distress syndrome (ARDS) worldwide. Two cautions apply to any such table. The frequencies are approximate and shift with the season, the age group and the sensitivity of the test used, so they describe typical patterns rather than fixed proportions. And detection of a virus in the upper tract does not prove it caused the illness, because several of these agents, notably rhinoviruses and adenoviruses, are shed asymptomatically.

The common cold (rhinitis)

The common cold is rhinitis with a variable degree of pharyngitis: nasal stuffiness, sneezing, rhinorrhoea and sore throat, often with chills but little fever, and sometimes cough or hoarseness. The pattern does not differ enough between agents to identify the virus clinically. Colds are among the commonest of all human experiences, with adults averaging two to four colds a year and young children six to eight; adults living with children, and women, are affected more often. They are self-limited, with a median illness of nine to ten days in adults and longer in children.

Rhinoviruses are the single commonest cause of colds, and their share looks larger still when detection relies on sensitive molecular methods such as reverse-transcriptase polymerase chain reaction (RT-PCR), which pick up infections that older culture-based tests miss. Coronaviruses account for a further share, mainly in winter, with RSV, hMPV and non-primary parainfluenza infections and, occasionally, a wider range of agents filling out the rest. Certain enteroviruses (coxsackievirus A21 and A24, echoviruses 11 and 20) cause febrile colds and sore throats in summer. The differential is limited, but high or persistent fever, respiratory distress or signs of lower-tract disease should prompt a search for an alternative diagnosis, and recurrent symptoms confined to the upper tract raise the possibility of allergy.

Most cold viruses spread by direct contact and self-inoculation of the nose and eyes as well as by respiratory droplets, which is why hand hygiene interrupts transmission.

The pathogenesis of the cold is instructive because symptoms are driven by the inflammatory response rather than by direct viral destruction of tissue. In rhinovirus infection only a small number of ciliated nasal epithelial cells are infected, the epithelial lining stays largely intact, and the number of infected cells is modest even when symptoms are marked. Nasal secretion early in the illness reflects increased vascular permeability, with glandular secretions (lactoferrin, lysozyme, secretory IgA) predominating later. Kinins and the cytokines interleukin-1, interleukin-6 and interleukin-8 rise in nasal secretions and correlate with symptoms, and instilled bradykinin reproduces the sore throat and blocked nose. Histamine, by contrast, plays little part, which is why selective (non-sedating) antihistamines do not work.

Colds are trivial in themselves but their complications are not. Otitis media and sinusitis follow when the inflammation obstructs the eustachian tube and sinus ostia: middle-ear pressure changes are documented after rhinovirus and influenza infection, cold viruses are found in a fifth to two-fifths of middle-ear effusions in children, and sinus mucosal abnormalities are visible on computed tomography in most people with a cold even though clinically manifest sinusitis is uncommon. Symptomatic otitis media complicates about 2% of colds in adults and a higher proportion in young children, while acute sinusitis is seen in only 0.5% to 5% of adults with colds.

Colds in atopic people tend to be more severe and more likely to provoke wheeze, and rhinoviruses are a major trigger of asthma exacerbations in children and adults and an important precipitant of exacerbations of chronic obstructive pulmonary disease (COPD).

Treatment is symptomatic and modest in effect: first-generation antihistamines and topical or oral decongestants ease rhinorrhoea and obstruction (the antihistamine benefit coming from anticholinergic rather than antihistamine action), ipratropium reduces watery nasal discharge, and non-steroidal anti-inflammatory drugs blunt the systemic symptoms. Antibacterial agents, echinacea and zinc offer no worthwhile benefit.

Pharyngitis

Pharyngitis, a sore throat with objective pharyngeal inflammation, is one of the commonest reasons for seeking care. The useful clinical division is between cases with nasal symptoms, which are predominantly viral, and those without, whose causes include group A and non-group A streptococci, mycoplasma, chlamydia and others. The presence of coryza or conjunctivitis favours a viral cause, whereas tonsillar exudate, tender cervical nodes, a scarlatiniform rash and absent coryza point towards streptococcal infection, though exudate also occurs with adenovirus and EBV. The anaerobe Fusobacterium necrophorum is now recognised as a frequent cause of pharyngitis in adults, resembling streptococcal disease and important because it underlies Lemierre syndrome. In children under three, pharyngitis is predominantly viral. A rapid antigen test for group A streptococci settles most uncertain cases and, when a sensitive assay is used, makes backup culture unnecessary, reducing needless antibiotics.

Several viruses give a recognisable picture.

Adenoviruses cause pharyngitis and, in types 3 and 7, pharyngoconjunctival fever (fever, pharyngitis and bilateral conjunctivitis).

Coxsackie A viruses cause herpangina, small vesicles on the soft palate that ulcerate. Influenza brings pharyngitis within an abrupt systemic illness of fever, myalgia and malaise.

Primary infection with herpes simplex virus (HSV) may present as pharyngitis with palatal vesicles and shallow ulcers. About half of the cases of infectious mononucleosis due to Epstein-Barr virus (EBV) feature an exudative pharyngitis with generalised lymphadenopathy, hepatosplenomegaly and a positive heterophile antibody in the second week; cytomegalovirus (CMV) produces an identical but heterophile-negative syndrome.

An acute mononucleosis-like illness with pharyngitis can also be the presenting feature of primary HIV infection, and the haemorrhagic fever viruses (Ebola, Marburg, Lassa) cause an early pharyngitis before skin signs appear.

The pathogenesis mirrors the cold: chemical mediators of inflammation stimulate pain endings, with direct viral damage contributing variably.

Treatment is usually symptomatic; influenzal pharyngitis seen within the first two days can be shortened by antiviral therapy, and aciclovir is used for primary herpetic gingivostomatitis and for herpetic pharyngitis in the immunosuppressed.

Antibiotic treatment of group A streptococcal pharyngitis shortens symptoms only modestly; its main purpose is to prevent the rheumatic complications that can follow untreated streptococcal infection.

Croup (laryngotracheobronchitis)

Croup is a distinctive illness of young children. After a day or two of coryza and sore throat the cough deepens into a brassy, barking, seal-like sound, and the hallmark sign is inspiratory stridor with prolonged inspiration. Fever is usual, the course fluctuates hour to hour, and the plain radiograph of the neck shows subglottic narrowing of the tracheal air column, the steeple sign.

Chest-wall retraction, hypoxaemia (present in around 80% of children admitted with severe croup) and rising carbon dioxide with fatigue mark the more severe end. Continuous pulse oximetry can be misleading, correlating poorly with respiratory distress and tending to increase admissions.

Croup is predominantly a disease of young children, peaking in the second year of life and somewhat commoner in boys; the annual incidence rises from around 5 per 1,000 in the first six months of life to nearly 15 per 1,000 in the second year, then falls sharply after age three.

Parainfluenza viruses cause about three-quarters of croup, types 1 and 2 most often, which is why the seasonal incidence tracks parainfluenza activity. RSV, influenza A and B, rhinoviruses, adenoviruses, the coronavirus NL63 and Mycoplasma pneumoniae account for most of the rest; measles is an uncommon but severe cause. Parainfluenza virus type 2 and influenza A tend to produce more severe disease, and severity broadly tracks the level of viral replication. The clinical syndrome is much the same whatever the agent, so specific viral diagnosis is not routine.

The critical task is to separate croup from the dangerous mimics of upper-airway obstruction: bacterial epiglottitis (acute distress and drooling without the barking cough, historically due to Haemophilus influenzae type b and now rare where the conjugate vaccine is used) and bacterial tracheitis, along with retropharyngeal abscess, diphtheria and an inhaled foreign body. Bacterial tracheitis, usually due to Staphylococcus aureus or Haemophilus influenzae type b, mimics croup but produces copious purulent sputum.

Distinguishing these can require direct visualisation of the epiglottis (with facilities for emergency airway management to hand) or a lateral neck radiograph showing a thickened, oedematous epiglottis; radiographs are limited in accuracy and are hazardous in a child in distress. A rapid response to nebulised adrenaline is itself suggestive of croup rather than a bacterial airway emergency.

The pathophysiology turns on the anatomy. Inflammation and oedema are greatest at the subglottis, the least distensible part of the airway because the cricoid cartilage encircles it, so localised swelling obstructs airflow and produces the high-pitched stridor; obstruction is worse on inspiration and in small children, whose airway walls are more compliant. Involvement of the lower tract is integral, and ventilation-perfusion (the matching of ventilation to blood flow, V/Q) mismatch, not obstruction alone, drives the hypoxaemia.

Management is largely supportive: oxygen for the hypoxaemic, corticosteroids (a single dose of dexamethasone or nebulised budesonide) which shorten symptoms and reduce admission and intubation, and nebulised adrenaline for rapid but short-lived relief in severe cases. Because the hypoxaemia arises from lower-tract V/Q mismatch rather than the airway narrowing alone, adrenaline relieves the stridor without correcting oxygenation, so treated children need close observation for rebound. Mist therapy, long popular, is of unproven value, and helium-oxygen mixtures remain of undetermined benefit; pulmonary oedema may follow relief of severe upper-airway obstruction, often just after intubation. Antibiotics have no role in a viral illness.

Tracheitis and tracheobronchitis

Viral infection of the trachea and bronchi below the larynx causes tracheitis and acute bronchitis. Tracheitis gives tracheal tenderness and substernal discomfort on inspiration; tracheobronchitis is dominated by a paroxysmal, non-productive cough that is worse at night and may later bring up small amounts of clear sputum, with fever, headache and myalgia. Chest signs are non-specific, usually scattered rhonchi and occasional wheeze; dullness, egophony or a friction rub should suggest pneumonia or effusion instead.

Influenza A and B are the typical causes, with parainfluenza, RSV, rhinoviruses and coronaviruses also implicated; HSV occasionally causes a necrotising tracheobronchitis with refractory bronchospasm. Influenza, rhinoviruses and coronaviruses also precipitate exacerbations of chronic bronchitis. The differential of a prolonged cough includes cough-variant asthma, Mycoplasma pneumoniae and Chlamydia pneumoniae, and Bordetella pertussis. In an otherwise healthy person the main task is to exclude pneumonia; treatment is symptomatic, and antibacterial agents give no benefit without evidence of a bacterial cause.

Bronchiolitis

Bronchiolitis is a syndrome of infants defined by its central defect, obstruction to expiratory airflow. Lower-tract symptoms are preceded by a day or two of rhinitis and then the hallmark wheeze, with nasal flaring, use of accessory muscles, a raised respiratory rate of 50 to 80 breaths a minute and hyperinflation that can push the liver down. Fever is often present early but absent by the time the chest is involved, so its absence does not reassure.

The radiograph shows air trapping, which is characteristic of RSV but does not track the clinical course; its main value is to exclude a bacterial pneumonia. Mild conjunctivitis accompanies about a third of cases, pharyngitis about half, and otitis media 5% to 10%, and most admitted infants improve within three to four days. Hyponatraemia can complicate severe disease, driven by the syndrome of inappropriate antidiuretic hormone secretion (SIADH), in which excess antidiuretic hormone causes water retention, and made worse if hypotonic fluid is given freely.

The differential of expiratory airflow obstruction in an infant is small but important: pertussis (suggested by paroxysmal cough, vomiting and lymphocytosis), the first presentation of asthma, an inhaled foreign body, a vascular ring and gastro-oesophageal reflux.

Bronchiolitis is a disease of infancy that closely follows the epidemiology of RSV, with a peak between two and six months and over 80% of cases in the first year. Around 10 per 1,000 infants are admitted in the first year of life, and the risk of severe disease is highest in those born prematurely or with congenital heart disease, chronic lung disease or immunodeficiency, and is also raised in infants under six weeks old, those exposed to cigarette smoke, and those with a family history of asthma; a higher viral load on a nasopharyngeal aspirate predicts intensive-care admission.

RSV causes the majority of cases and, during its epidemic season, almost all of them, and is recovered from about three-quarters of infants admitted with bronchiolitis. Human metapneumovirus produces a clinically indistinguishable illness; rhinoviruses are the next most commonly detected (with the caveat that they are also found in asymptomatic children); and parainfluenza, influenza, adenovirus (types 3, 7 and 21, which can cause bronchiolitis obliterans), the coronavirus NL63 and human bocavirus make up the remainder.

The pathophysiology is best described for RSV. Infection destroys the ciliated epithelium of the bronchioles, the submucosa becomes oedematous, and mucus production rises until dense plugs of debris and fibrin obstruct the small airways; hypoxaemia from V/Q mismatch is the major gas-exchange abnormality.

Infants are peculiarly vulnerable because their peripheral airways are disproportionately narrow, their collateral channels of ventilation few, and their airways intrinsically more reactive. The immune response contributes to injury: overproduction of immunoglobulin E, a shift in the cytokine profile of responding T cells, and release of leukotrienes have all been implicated, and single-nucleotide polymorphisms in inflammatory genes (among them those for interleukin-4, interleukin-8, interleukin-13, the Toll-like receptor TLR-4 and the CCR5 receptor) influence severity.

A documented episode of RSV lower-tract disease is followed by a roughly three- to fourfold increase in later wheezing, though whether the infection causes the airway tendency or merely unmasks it is unresolved.

Management is supportive, centred on correcting hypoxaemia; bronchodilators, systemic corticosteroids and antibiotics do not help routine bronchiolitis. Nebulised hypertonic saline may modestly reduce admissions, and a humidified high-flow nasal cannula or continuous positive airway pressure can support infants at risk of respiratory failure. Careful attention to fluids and electrolytes matters, since over-generous hypotonic fluid can worsen the hyponatraemia of SIADH.

Prevention has changed substantially. The monoclonal antibody palivizumab, given monthly to high-risk infants, has been largely superseded by nirsevimab, a single long-acting monoclonal antibody that protects for a whole season and is offered to all infants, and by a maternal RSV vaccine given in pregnancy to protect the newborn through transplacental antibody.

There is still no vaccine against parainfluenza, and an RSV vaccine was for decades held back by the memory of an early formalin-inactivated preparation that worsened rather than prevented disease in vaccinated infants, a caution that shaped the long path to today’s maternal vaccine and monoclonal antibodies. Nosocomial RSV spread, an important hazard on infant and transplant wards, is limited by hand hygiene, surface decontamination, and gowns, gloves and eye protection.

Viral pneumonia

Pneumonia is inflammation of the lung parenchyma with impaired alveolar gas exchange, usually with radiographic change. The viral pneumonia clinical picture is highly variable, but some general features recur: the patient looks acutely ill, the respiratory rate is raised with diffuse crackles and often wheeze, and the sputum is scant with few neutrophils and few bacteria on Gram stain. In children the picture is fever with difficulty breathing, non-productive cough and wheeze, and young infants may present simply with apnoea.

Several factors raise the risk or severity of viral pneumonia: underlying cardiopulmonary disease, neuromuscular conditions that impair clearance of secretions, obesity, immunocompromise, and, notably for influenza, pregnancy, which was strikingly over-represented among severe cases in the 2009 A(H1N1) pandemic and remains a risk through pregnancy and the puerperium.

Bacterial superinfection is the major complication in adults. The classic course is a typical viral illness with near-complete recovery, then a return of fever, cough and dyspnoea 2 to 14 days later with lobar consolidation. Streptococcus pneumoniae is the commonest superinfecting organism after influenza, with Staphylococcus aureus (including methicillin-resistant strains, MRSA) and Haemophilus influenzae also important. Combined viral and bacterial pneumonia, carrying features of both at once, is equally common.

The spectrum of viral pneumonia otherwise depends heavily on age and immune status, differing between immunocompetent adults, children and the immunocompromised host.

Immunocompetent adults

Pure viral pneumonia is relatively uncommon in healthy adults, but sensitive molecular tests detect a virus in 20% to 30% of community-acquired pneumonia, and in as many as a third of adults with acute pneumonia when the most sensitive assays are used, frequently alongside a bacterium. Influenza is the best-recognised cause, mainly during seasonal epidemics.

RSV is the most frequently detected agent overall and is increasingly recognised as a cause of serious lower-tract disease in the elderly, in whom it is estimated to account for 2% to 4% of pneumonia deaths; even short of pneumonia, RSV commonly produces measurable airway reactivity in adults.

Adenoviruses cause outbreaks of pneumonia in military recruits, historically serotypes 4 and 7 and more recently the severe serotype 14; the illness resembles mycoplasma pneumonia but can produce large pleural effusions and, occasionally, disseminated fatal disease.

Varicella pneumonia is more severe in adults, particularly smokers and in pregnancy: infiltrates appear in 10% to 20% of adults with chickenpox, typically nodular and peribronchial, and their severity tracks the diffuseness of the rash rather than the chest findings, with diffuse pulmonary calcifications a recognised late sequela.

Measles can cause a severe pneumonitis in a small proportion of healthy adults, commonly with bacterial superinfection, and acute EBV mononucleosis is occasionally complicated by a diffuse pneumonitis and respiratory failure; parainfluenza viruses are an occasional cause of pneumonia in the elderly.

Two more recent entries dominate current practice. Hantaviruses cause hantavirus cardiopulmonary syndrome, in which a brief influenza-like prodrome is followed by rapid pulmonary oedema and shock driven by immune-mediated capillary leak; the absence of coryza, together with early interstitial oedema and thrombocytopenia with haemoconcentration, helps separate it from ARDS of other cause.

The betacoronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 cause severe pneumonia and ARDS; SARS-CoV-2, the cause of COVID-19, is now among the leading causes of viral pneumonia and respiratory failure in adults worldwide.

Children

Viruses are the dominant causes of pneumonia in young children, detected in around two-thirds of radiographic pneumonia, and their contribution falls after age five. RSV accounts for the largest share in the young, frequently coexisting with bronchiolitis as one spectrum of lower-tract disease; the usual radiographic picture is a diffuse interstitial pneumonitis, with lobar or segmental consolidation in about a quarter, often in the right upper or middle lobe.

Parainfluenza viruses, especially type 3, come next, followed by influenza A and B, which carry a higher risk of secondary bacterial pneumonia than RSV or parainfluenza. Rhinoviruses are frequently detected but also common in asymptomatic children, complicating attribution. Adenoviruses account for around a tenth of childhood pneumonias, often with hilar adenopathy, though prolonged asymptomatic shedding blurs their true impact.

Pneumonia is the commonest serious complication of measles, whose prodrome of fever, cough, coryza and conjunctivitis with Koplik spots precedes the rash; a pronounced leukopenia (under 2,000 cells per cubic millimetre) carries a poor prognosis, and a new neutrophil leukocytosis suggests bacterial superinfection. Cytomegalovirus causes pneumonia in premature infants lacking maternal antibody, and enterovirus D68 has emerged as a cause of severe paediatric respiratory illness.

Immunocompromised hosts

The immunocompromised are vulnerable to the whole spectrum of respiratory viruses, including opportunists that spare the immunocompetent, and the DNA viruses are prominent. Cytomegalovirus is a frequent cause of severe pneumonitis in transplant recipients, with the greatest risk one to three months after transplantation and a peak around eight weeks; a diffuse interstitial pneumonitis is typical, and accompanying neutropenia, deranged liver enzymes and mucosal ulceration point to the disseminated infection behind it.

Herpes simplex virus pneumonia occurs in debilitated and immunosuppressed patients, most often as a focal pneumonia from contiguous spread but as diffuse haematogenous disease in up to 40%, with neonates, transplant and burns patients and the ventilated at risk. Disseminated varicella-zoster virus causes pneumonia in haematological malignancy and transplantation, heralded by prolonged fever and recurrent crops of lesions and sometimes pleuritic pain from pleural vesicles. Adenovirus infection tends to disseminate across multiple organs, with virus recoverable from lung, liver, gut and urine.

The community respiratory viruses are increasingly recognised here too: RSV pneumonia in haematopoietic stem-cell transplant recipients carries a mortality of 50% or more, particularly before engraftment, and parainfluenza and influenza also cause severe disease. Measles giant-cell pneumonia is a usually fatal illness of the profoundly immunosuppressed and the severely malnourished, in whom the typical rash may be absent.

Pathogenesis

The pathogenesis of viral pneumonia falls into three patterns. In primary viral pneumonia, taking influenza as the model, virus reaches the lung by contiguous spread or aerosol inhalation and destroys the ciliated epithelium of the trachea, bronchi and bronchioles; the alveoli fill with neutrophils, mononuclear cells, fibrin and oedema fluid, capillaries become hyperaemic with haemorrhage, and hyaline membranes line the alveolar ducts, the picture of diffuse alveolar damage. In the second pattern, respiratory infection disseminates to cause systemic disease with lung involvement, as in measles and varicella. In the third, the lung is involved secondarily within a systemic infection, as with cytomegalovirus in the transplant recipient. Hantavirus cardiopulmonary syndrome is a distinct mechanism: widespread infection of vascular endothelium, most intense in the lung, produces immune-mediated capillary leak rather than cytolysis.

Bacterial superinfection is favoured by loss of the epithelial barrier and mucociliary clearance, increased bacterial adherence to infected cells, and impaired leukocyte function.

Diagnosis

Attributing a respiratory illness to a specific virus is complicated by the difficulty of sampling the lower tract and by the frequent asymptomatic shedding of rhinoviruses, adenoviruses and herpesviruses in the upper tract. Clinical presentation, season and associated features such as a rash give useful clues, particularly in children, but rarely identify the agent alone.

Multiplex nucleic acid amplification (polymerase chain reaction, PCR) is now the central diagnostic method in well-resourced settings, detecting a wide panel of viruses in upper- and lower-tract samples; a nasopharyngeal aspirate is superior to a swab. Its main interpretive trap is that detecting a virus neither excludes a coexisting bacterial infection nor proves that antibacterial therapy can be withheld.

Rapid antigen tests are quicker but less sensitive, and their yield depends on specimen quality, a nasopharyngeal aspirate again outperforming a swab. Radiology does not reliably separate viral from bacterial pneumonia, and biomarkers such as procalcitonin and C-reactive protein have only modest power to do so, though a high procalcitonin raises the probability of bacterial infection.

The purpose of testing shapes how far to pursue it. For the self-limited upper-tract syndromes and for croup the clinical picture usually suffices and the specific virus does not change management, so identification is directed instead at infection control, protecting vulnerable contacts, and epidemic surveillance, where naming the circulating strain of influenza or confirming RSV or SARS-CoV-2 matters. In severe lower-tract disease, in the immunocompromised, and in outbreaks, a specific diagnosis guides antiviral choice, isolation and public-health response, and justifies the more invasive lower-tract sampling that attribution of pneumonia often requires.

Management and prevention

Management is largely supportive, and its depth belongs with the individual viruses; the principles are consistent. Correcting hypoxaemia is the priority in severe lower-tract disease, escalating to high-flow oxygen, non-invasive support and, in the worst cases, mechanical ventilation or extracorporeal membrane oxygenation. Early corticosteroids generally worsen viral pneumonia (croup and severe COVID-19, where they clearly help, are the exceptions), and antibacterial cover is added when bacterial superinfection is suspected.

Specific antivirals are few. Influenza is treated with the neuraminidase inhibitors (oseltamivir, zanamivir, peramivir) or the cap-dependent endonuclease inhibitor baloxavir, most effective within 48 hours of onset but with an observed mortality benefit when started later in hospitalised patients; the older M2 inhibitors are obsolete because circulating strains are resistant. SARS-CoV-2 is treated with agents such as nirmatrelvir-ritonavir and remdesivir in those at risk of severe disease. Ribavirin has limited evidence and is reserved mainly for RSV or measles in the immunocompromised, sometimes combined with immunoglobulin and given early while upper-tract symptoms predominate; DAS-181, an inhaled sialidase, has shown anecdotal benefit against parainfluenza in transplant recipients.

Prevention rests on vaccination and infection control. Annual influenza vaccination and COVID-19 vaccination are the mainstays for those at risk, and RSV is now preventable in infants by nirsevimab or maternal vaccination and in older adults by the newer RSV vaccines. There is still no licensed vaccine against parainfluenza, rhinovirus or human metapneumovirus. Droplet and contact precautions, hand hygiene and cohorting limit spread, and the prevention of nosocomial RSV and influenza on paediatric and transplant units is a particular priority.

South African context

Respiratory viruses in South Africa follow a Southern Hemisphere calendar, with the influenza season falling in the middle of the year and RSV circulating somewhat earlier; the National Institute for Communicable Diseases (NICD) tracks both through sentinel programmes for influenza-like illness (the Viral Watch network) and severe respiratory illness. Sentinel surveillance for severe acute respiratory illness and for pneumonia-associated deaths has confirmed RSV and influenza as the leading viral contributors, with RSV activity typically preceding the influenza season each year.

The burden of severe disease is shaped by the country’s large populations of people living with HIV and of HIV-exposed infants, in whom respiratory viral pneumonia is more frequent and more severe, and by tuberculosis co-infection, which enters the differential of any subacute respiratory illness. Childhood pneumococcal and Haemophilus influenzae type b conjugate vaccination, now embedded in the Expanded Programme on Immunisation, has reduced the bacterial disease that complicates viral lower-tract infection.

Influenza vaccination is directed at defined priority groups, including pregnant women, people living with HIV, those with chronic medical conditions, the elderly and healthcare workers, and antiviral treatment is guided by the current NICD recommendations. RSV immunoprophylaxis is not yet part of the public immunisation programme, and COVID-19 vaccination continues to target those at highest risk of severe disease.

References and recommended reading

• Treanor JJ. Respiratory Infections. In: Richman DD, Whitley RJ, Hayden FG, editors. Clinical Virology, 4th edition, Chapter 2. Washington: ASM Press; 2016. The backbone source for the respiratory syndromes, their viral causes, and the pathogenesis and clinical features of each.
• Burrell CJ, Howard CR, Murphy FA. Viral Diseases of the Respiratory Tract. In: Fenner and White’s Medical Virology, 5th edition, Chapter 39. Academic Press / Elsevier; 2017. The source for the six-syndrome gradient and the adapted syndrome-to-virus table.
• National Institute for Communicable Diseases (NICD). Influenza: NICD recommendations for the diagnosis, management, prevention and public health response, version 1.8. Johannesburg: NICD; 2026. The current South African reference for influenza diagnosis, antiviral treatment, vaccination priority groups and surveillance.