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Respiratory infection—viral 

Respiratory infection—viral
Chapter:
Respiratory infection—viral
Author(s):

Stephen Chapman

, Grace Robinson

, John Stradling

, Sophie West

, and John Wrightson

DOI:
10.1093/med/9780198703860.003.0044
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date: 30 November 2021

Overview of viral pneumonia

  • Viral URTIs are common, but typically self-limiting, and are usually managed in the community. Viral pneumonia is less common but is more serious and usually requires hospitalization. Viral pneumonia in the immunocompetent is rare and typically affects children or the elderly; influenza strains are the commonest cause in adults. Studies suggest that viruses are detectable in 15–30% of patients hospitalized with pneumonia

  • Viruses may cause serious respiratory infection in the immunocompromised (particularly patients with depressed T-cell function, e.g. following organ transplantation). CMV is the commonest serious viral pathogen that affects immunocompromised patients. Influenza, parainfluenza, RSV, measles, and adenovirus may also cause pneumonia in the immunocompromised, although diagnosis of these viruses is difficult and infection is commonly undetected

  • The clinical and radiological features of viral pneumonia are non-specific. Worsening cough and breathlessness following an URTI suggest the development of pneumonia; wheeze may accompany bronchiolitis. CXR typically shows non-specific diffuse interstitial infiltrates, and hypoxia may occur. 2° bacterial infection may complicate viral pneumonia

  • A variety of diagnostic techniques are available, including PCR, viral culture, antigen testing (e.g. EIA and direct fluorescent antibody (DFA) testing), and serology

  • Treatment consists of supportive care and, in some cases, antivirals. Infection with certain viruses may require isolation. Treat 2° bacterial infection with antibiotics

  • Specific features of the common and/or important viruses are noted in the remainder of the chapter.

Influenza: background

  • Single-stranded enveloped RNA viruses

  • Commonest cause of viral pneumonia in immunocompetent adults. It is transmitted via respiratory secretions and is extremely contagious

  • Three pathogenic serotypes: A, B, and C. Type A causes more severe disease and occurs in annual epidemics and intermittent pandemics. Types B and C cause epidemics

  • The surface antigens haemagglutinin and neuraminidase determine influenza serotype. Genetic mutations may result in antigenic shifts (major genetic rearrangements between strains, associated with pandemics of influenza A—1918 (H1N1), 1957 (H2N2), 1968 (H3N2), and 2009 (H1N1) pandemics) and antigenic drifts (more minor genetic variations associated with epidemics)

  • Genetic rearrangement of virus occurs in animal and bird reservoirs, and the virus may then be transferred to humans, e.g. 2009 H1N1 was caused by reassortment of two swine, one human, and one avian strains

  • Seasonal influenza is very well recognized in the UK, particularly during the winter months. Seasonal influenza may affect previously well individuals, although it occurs more commonly in the elderly, particularly in the setting of chronic heart or lung disease or immunocompromise

  • Pandemic 2009 influenza A/H1N1 was first detected in Mexico and lasted until August 2010, affecting >214 countries and territories and an estimated 201, 000 respiratory deaths associated with influenza (18, 500 of these were laboratory-confirmed cases). The majority of infection and deaths occurred in those aged 18–64 years old, with lower rates in elderly patients probably due to exposure to similar strains earlier in life. High death rates particularly seen in pregnant patients

  • Outbreaks of highly pathogenic H5N1 avian influenza have occurred in many countries, raising fears of the development of sustained human-to-human transmission and a new global pandemic. >600 cases have been reported worldwide since 2003, associated with a 60% mortality

  • Novel avian influenza A/H7N9 was first reported in March 2013 in eastern China, with likely transmission via secretions/excretions of infected poultry, with no evidence (as yet) of sustained human-to-human transmission. Serological studies have found no evidence of human infection with novel H7N9 prior to November 2012 in Chinese poultry workers. The virus seems to have been created by reassortment of at least four avian influenza viruses (probably obtaining its haemagglutinin gene from H7N3 in domestic ducks, its neuraminidase gene from H7N9 in wild birds, and six remaining genes from multiple related H9N2 viruses in domestic poultry). Early reports suggest that the median patient age is ~60 years old (contrasted with median H5N1 patient age of ~25 years old) and is associated with a 27% mortality.

Regularly updated information on seasonal, avian, and pandemic influenza is available from the Health Protection Agency, the World Health Organization, and the US Centers for Disease Control and Prevention websites:

Additional guidelines are available for the management of suspected influenza in the setting of a pandemic with UK Pandemic Alert Levels 2–4 (cases of pandemic influenza identified in UK):

Influenza: diagnosis

Clinical and laboratory features

Incubation period typically 1–4 days; adults contagious for 7 days and children for 21 days from illness onset. The clinical picture following infection is variable and may be influenced, in part, by the influenza subtype. Features include:

  • Asymptomatic infection

  • ‘Flu’ (acute onset of fever, cough, headache, coryzal symptoms, myalgia, sore throat)

  • Complications include:

    • Bronchitis/bronchiolitis

    • influenza viral pneumonia (onset typically within 48h of initial fever; cough dry or productive, haemoptysis may occur, bilateral crackles, and/or wheeze; may progress very rapidly to respiratory failure and death; described in many patients infected with avian influenza H5N1 and H7N9 and more likely among pandemic H1N1 than for seasonal influenza; often associated with lymphopenia, thrombocytopenia, abnormal liver function, and multi-organ failure)

    • bacterial pneumonia (significantly more common than viral pneumonia; onset typically 4–5 days after initial fever, during early convalescence, although may occur earlier; pathogens include S. pneumoniae, S. aureus—particularly associated with lung abscess—and H. influenzae; mixed bacterial/viral pneumonia may occur)

    • GI symptoms (e.g. watery diarrhoea; more frequently described during influenza A H1N1 and avian H5N1 than seasonal infection)

    • Otitis media (particularly in children), conjunctivitis; rarely parotitis

    • Myositis (CK may be elevated; rarely myoglobinuria with renal failure)

    • Neurological (encephalitis, acute necrotizing encephalopathy, transverse myelitis, Guillain–Barré syndrome—all rare; Reye’s syndrome with encephalopathy and fatty liver following aspirin use is well described in children and adolescents)

    • Cardiovascular (ECG abnormalities common, myocarditis or pericarditis rare).

Imaging

  • CXR typically shows bilateral mid-zone interstitial infiltrates in 1° viral pneumonia, although focal consolidation is also well described. Lobar consolidation occurs in 2° bacterial pneumonia.

Differential diagnosis

of ‘flu-like’ illness includes adenovirus, RSV, rhinovirus, parainfluenza, Chlamydophila pneumoniae, Legionella, Mycoplasma, and S. pneumoniae. A very high fever is said to favour a diagnosis of influenza. Consider Middle East respiratory syndrome (MERS) (see Respiratory infection—viral p. [link]) in patients with an appropriate travel history.

Diagnosis

is often suggested by knowledge of a local outbreak. Diagnostic investigations include:

  • Virology (not routinely required if pandemic established with widespread infection across the UK—Alert Level 4—when diagnosis will be clinical—‘influenza-like illness’)

    • Presentation <7 days after illness onset: nose and throat swabs in virus transport medium (for direct immunofluorescence, ELISA, virus culture, and/or reverse transcriptase PCR (RT-PCR))

    • Presentation >7 days after illness onset: ‘acute’ serum and subsequently ‘convalescent’ serum after 10–14 days (for influenza serological testing)

  • Bacteriology (in patients with influenza-related pneumonia)

    • Blood culture

    • Pneumococcal and Legionella urinary antigen

    • Sputum M, C, & S (if purulent sputum and either no prior antibiotics or failure to respond to empirical antibiotics)

    • ‘Acute’ serum and subsequently ‘convalescent’ serum after 10–14 days for influenza/other agents serological testing.

Influenza: management

Severity assessment

  • Patients with uncomplicated influenza do not require admission

  • For influenza-related pneumonia, a CURB-65 score (see Respiratory infection—viral pp. [link][link]) of ≥3 indicates severe pneumonia and a high risk of death; patients with a score of 0 or 1 may be considered for home treatment

  • Bilateral CXR infiltrates consistent with 1° viral pneumonia should be considered as severe pneumonia, irrespective of CURB-65 score.

Infection control

  • Outside the setting of a UK pandemic, most suspected cases of influenza are likely to be seasonal

  • H5N1 avian influenza should be seriously considered in patients with:

    • Fever (≥38°C) and lower respiratory tract symptoms or CXR showing consolidation/ARDS or a severe illness suggestive of an infectious process, and

    • Close contact (<1m) within 7 days with either live or dead domestic poultry or wild birds in countries affected by H5N1 (or known infected animals, e.g. cats or pigs) or close contact with human cases of severe unexplained respiratory illness or unexplained illness resulting in death in patients from countries with H5N1

  • H7N9 avian influenza should be suspected in patients with:

    • Fever (≥38°C) and clinical or CXR findings of consolidation/ARDS or a severe illness suggestive of an infectious process, and

    • Travel to China within 10 days before symptom onset

In such cases of suspected avian influenza, the patient should be assessed either at their home or in a hospital side room, with both patient and staff wearing surgical masks and staff wearing gown and gloves. Immediately inform local Health Protection Unit as well as hospital infection control and occupational health. If hospitalization is required, patients should be in strict respiratory isolation, preferably in a negative pressure room (although patients should not be transferred for this reason alone), and staff should wear high-filtration mask (FFP3), gown, gloves, and eye protection (consider also cap and plastic apron, depending on situation). Mark all laboratory samples as ‘high risk’, and inform local laboratory of the sample status.

Treatment

  • Supportive care O2, IV fluids, nutritional support. Consider ITU/HDU admission for patients with one or more of more of: 1° viral pneumonia; CURB-65 score of 4 or 5; PaO2 <8kPa despite high-flow O2; progressive hypercapnia; pH <7.26; septic shock. NIV may be used for patients with COPD and decompensated type II respiratory failure, although infection control measures should be in place and protective equipment worn by staff to minimize any spread of infection from respiratory droplets

  • Antiviral treatment with neuraminidase inhibitors is indicated for patients with an influenza-like illness and fever >38°C within 48h of symptom onset; consider also treating immunocompromised or very elderly patients in the absence of fever, and severely ill or immunocompromised patients if >48h from disease onset. Also treat patients with suspected H5N1 or H7N9, regardless of duration of symptoms. Treat with: oseltamivir 75mg bd for 5 days (75mg od if creatinine clearance <30mL/min); anti-emetics may be needed for nausea. Inhaled zanamivir 10mg bd via inhaler for 5 days (up to 10 days if resistance to oseltamivir) is another option for non-severe disease. Antivirals appear to reduce illness duration (by 1 day), hospitalization, and subsequent antibiotic requirements; possible effects on mortality have not been adequately studied. The neuraminidase inhibitor zanamivir may be given intravenously (e.g. for ventilated patients), but its effectiveness in this situation is unproven. Antiviral prophylaxis may be considered for health care workers caring for patients with suspected avian influenza, as well as the patient’s household contacts

  • Treat influenza-related pneumonia with antibiotics, according to severity, e.g. oral co-amoxiclav, a tetracycline (e.g. doxycycline), or a macrolide if non-severe; IV co-amoxiclav or cefuroxime or cefotaxime, together with a macrolide, if severe.

Outcome

Uncomplicated influenza typically resolves within 7 days, although cough and malaise may persist for several weeks. The reported mortality from 1° influenza viral pneumonia is >40% and up to 24% from 2° bacterial pneumonia. Risks of viral pneumonia are increased in older patients with cardiorespiratory disease or diabetes. Pandemics are associated with a shift in the age distribution—the 2009 pandemic saw high rates of mortality and morbidity among children and young adults.

Vaccination

  • The influenza inactivated vaccine is modified annually, based on recent viral strains (and now includes antigen from the 2009 pandemic H1N1), and provides partial protection against influenza illness, hospitalization, and death. Vaccination if age >65, chronic comorbidity, nursing home residents, or health workers. Vaccination will not protect against H5N1 avian influenza but may make simultaneous co-infection with human and avian influenza less likely and so reduce the likelihood of viral genetic reassortment

  • Administration of oseltamivir 75mg od to high-risk individuals throughout periods of exposure may also prevent infection

  • Live attenuated influenza vaccines are currently under investigation.

Further information

Gao et al. Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med 2013;368:2277–85.Find this resource:

Gao et al. Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 2013;368:1888–97.Find this resource:

Cytomegalovirus pneumonia

Epidemiology

  • Enveloped dsDNA virus

  • CMV is the commonest serious viral pathogen in the immunocompromised and is a particular problem following transplantation where prophylaxis is now widely used

  • Individuals are described as ‘seropositive’ for CMV if they have evidence of IgG antibodies, indicating latent infection following previous exposure; seropositivity increases with age. Infection in transplant recipients results from either transmission from a CMV positive donor to a CMV antibody negative recipient (via the organ or a blood transfusion) or reactivation of latent CMV in a seropositive recipient as a result of immunosuppression

  • Infection occurs most frequently during the first 4 months following organ or bone marrow transplantation, corresponding to the period of maximal T-cell suppression. GVHD increases the risk of CMV infection.

Clinical and laboratory features

  • ‘Flu-like’ symptoms in immunocompetent patients

  • Symptoms of CMV pneumonia in the immunocompromised are non-specific: fever, dry cough, dyspnoea, and malaise

  • Extrapulmonary manifestations of CMV infection (e.g. gastro-oesophagitis; hepatitis) may suggest the diagnosis

  • Hypoxia may occur. Leucopenia, thrombocytopenia, and abnormal LFTs are characteristic.

Imaging

  • CXR Typically bilateral diffuse interstitial infiltrate, although lobar consolidation and localized haziness also described; can be normal. A nodular infiltrate may suggest co-infection with Aspergillus

  • CT Features include localized or diffuse ground-glass and nodular shadowing that may progress to airspace consolidation.

Diagnosis

Antibody tests are used to estimate risk following transplantation, but diagnosis of active disease requires evidence of either viraemia (by antigen or PCR testing of blood) or tissue invasion (by biopsy). A wide range of diagnostic tests are available, and the choice of tests varies between centres—discuss with your local virologist. The nature of the transplant and immunosuppression also influence the interpretation of test results. Methods include:

  • Early antigen fluorescence test on BAL fluid (high sensitivity, low specificity)

  • Qualitative PCR on blood or BAL fluid (highly sensitive but unable to differentiate between latent and replicating CMV; negative result practically excludes the diagnosis, positive result is unhelpful)

  • CMV antigenaemia on blood (rapid, differentiates between latent and replicating virus)

  • Quantitative PCR on blood or BAL fluid (rapid, differentiates between latent and replicating virus)

  • Indirect immunofluorescence with monoclonal antibodies to CMV in BAL fluid (rapid, highly sensitive, and specific)

  • Histology of lung tissue from transbronchial or surgical biopsies (demonstrate CMV inclusion bodies—the ‘owl’s eye’ appearance—within infected cells; considered gold standard investigation).

In some cases, a definitive diagnosis is not possible and treatment is empirical.

Treatment

Reduce immunosuppression where possible. Ganciclovir 5mg/kg IV bd for 2–4 weeks (side effects include neutropenia, anaemia). Consider additional treatment with anti-CMV hyperimmune globulin or prolonged oral valganciclovir in cases of severe or relapsed disease. Foscarnet 60mg/kg tds for 2–3 weeks is an alternative to ganciclovir for resistant cases, but toxicity (nephrotoxicity, metabolic disturbance) can limit treatment.

Complications

  • Opportunistic infection (e.g. PCP, aspergillosis) due to further suppression of T-cell function by the CMV infection itself

  • Increased risk of organ rejection, as allografts are more susceptible to CMV infection than native organs.

Outcome

The reported mortality from CMV pneumonia varies although may be as high as 85%. Relapse occurs in up to one-third of patients.

Adenovirus

  • Non-enveloped dsDNA viruses

  • Worldwide distribution, occur throughout the year

  • >50 serotypes, the relative frequency of which is unclear. Some studies suggest serotypes 1–3 are most common, but studies in the armed services found high frequencies of serotypes 4, 7, and 14 (all of these are associated with upper and lower respiratory tract infections)

  • Most common symptoms are those of self-limiting upper airways infection, which frequently mimics group A streptococcal infection, particularly in childhood

  • Can cause pneumonia and ARDS in adults

  • Occasional complications—myocarditis, hepatitis, nephritis, meningoencephalitis, and DIC

  • Disseminated disease may occur in the immunocompromised (sometimes due to virus reactivation)

  • Diagnosis is by nasopharyngeal fluid, sputum, or BAL fluid viral culture, antigen testing or PCR, or quantitative PCR on blood (particularly in the immunocompromised). Serology and histology (showing intranuclear inclusions) may also be helpful

  • Treatment is usually supportive, but the seriously unwell (particularly the immunocompromised) may be treated with cidofovir (unlicensed; nephrotoxicity; poor evidence) ± IV immunoglobulin. Ganciclovir has limited activity against adenoviruses.

Measles

  • Enveloped single-stranded RNA virus

  • Very rare in adults. Symptomatic respiratory involvement (e.g. croup, bronchiolitis, and pneumonia) occur most commonly in the very young and those >20 years old and is a common cause of mortality

  • Symptoms of fever and URTI are followed by a diffuse maculopapular rash. Leucopenia is common

  • CXR may show reticulonodular infiltrates, hilar lymphadenopathy, and pleural effusions

  • 2° bacterial infection is common

  • Diagnosis is serological; viral culture is possible but rarely performed

  • Treatment is supportive. Treat 2° bacterial infection with antibiotics.

Human metapneumovirus

  • Single-stranded enveloped RNA virus

  • First isolated in 2001, ubiquitous worldwide

  • Seasonal variation—peaks in late winter and early spring

  • Most children are infected by 5 years old

  • Usually causes mild self-limiting upper airways infection ~5 days after infection but may progress to wheezing and pneumonia or ARDS in some adults (especially the immunocompromised or elderly patients with comorbidities)

  • Ongoing airways hyperreactivity may last for several weeks

  • PCR/serological evidence of metapneumovirus in ~4% of adults admitted with acute lower respiratory tract infection

  • Diagnosis is usually using in full reverse transcriptase PCR (RT-PCR), serology, or viral culture of nasopharyngeal or BAL specimens

  • Treatment is supportive. Ribavirin may have activity in vivo, but this is still under investigation.

Parainfluenza

  • Single-stranded enveloped RNA viruses; serotypes 1–4

  • >90% of adults have antibodies to parainfluenza, but these are only partially protective

  • Types 1–3 usually cause self-limiting upper respiratory infection but can cause pneumonia, particularly among the elderly or immunocompromised. Type 4 usually causes URTI

  • Associated with asthma and COPD exacerbations

  • Rarely causes myocarditis, meningitis, and Guillain–Barré syndrome

  • Diagnosed using PCR, antigen detection, or viral culture on nasopharyngeal secretions or BAL fluid

  • Treatment is supportive, with reduction of immunosuppression (particularly glucocorticoids) when possible.

Respiratory syncytial virus

  • Single-stranded enveloped RNA virus; subtypes A and B. Subtype A is associated with more severe disease

  • Very common cause of bronchiolitis and pneumonia in children, causing winter outbreaks. Role in adult respiratory disease is more significant than previously appreciated, and infection often goes unrecognized, with ~5% of adults developing RSV each year

  • Clinical features in adults are usually of URTI or tracheobronchitis, but this may progress to pneumonia, particularly in the setting of underlying cardiac or respiratory disease, malignancy, or immunosuppression; outbreaks affecting adults in hospitals and nursing homes also occur. RSV may be a relatively common viral cause of pneumonia in patients who have recently undergone bone marrow transplantation

  • Nasopharyngeal secretions and BAL fluid are often diagnostic; detection of RSV antigen in BAL fluid has a sensitivity of nearly 90%. PCR-based diagnostic techniques and serological testing may have a role

  • Bacterial superinfection may be a frequent complication

  • Treatment is principally supportive. Role of aerosolized ribavirin and steroids in the treatment of severe disease in adults is unclear. Reports of successful outcomes in bone marrow transplant recipients following treatment with ribavirin and immunoglobulin.

Varicella pneumonia

  • Caused by varicella-zoster virus (an enveloped dsDNA virus)

  • Pneumonia occurs in a small proportion of adults with chickenpox or shingles but accounts for the majority of mortality associated with adult disease. Risk factors for its development include smoking, increased number of skin spots (>100), pregnancy (third trimester), steroid treatment, and immunocompromise

  • There is typically a history of recent exposure to a contact infected with chickenpox or shingles. Chest symptoms tend to occur several days after the onset of rash (erythematous macules progressing to papules and then vesicles), although rarely may precede the rash. Cough and breathlessness are common, and pleuritic pain and haemoptysis may occur

  • CXR typically shows a diffuse small nodular infiltrate; hilar lymphadenopathy and pleural effusions may uncommonly occur. Nodules may subsequently calcify and persist

  • Multi-organ involvement may occur

  • Diagnosis is usually suspected on the basis of the history of exposure, presence of rash, and CXR features. Cytological examination of smears from skin lesions, serology, or viral culture or PCR on BAL fluid may confirm the diagnosis

  • Treatment of varicella pneumonia is with early administration of aciclovir 10–12.5mg/kg IV tds for 7–10 days. Aciclovir is not licensed for use in pregnancy but does not appear to be associated with increased foetal abnormalities, and the benefits of treatment almost certainly outweigh any risk. Varicella is very infectious until lesions enter the ‘crusting’ stage; inpatients should be isolated. Extracorporeal membrane oxygenation/life support has been used successfully in individuals with fulminant respiratory failure. Consider early administration of varicella-zoster immune globulin for immunocompromised and pregnant patients exposed to varicella

  • Most cases resolve spontaneously, but a minority progresses to respiratory failure and death (10–30%). Mortality may be significantly higher in pregnancy.

Hantavirus pulmonary syndrome

  • Also known as hantavirus cardiopulmonary syndrome

  • Caused by single-stranded enveloped RNA hantaviruses

  • First described following an outbreak in the south-western USA in 1993. Several different hantaviruses (e.g. Sin Nombre virus) have been associated with this syndrome. Previously described hantavirus-associated diseases occurred more commonly in Scandinavia and north-eastern Asia and tended to cause haemorrhagic fever and renal failure, with relative sparing of the lung

  • Very rare, and affected individuals are almost exclusively from America, particularly from the Four Corners Region of USA where Arizona, Colorado, Utah, and New Mexico meet. A 2012 outbreak, affecting ten people who visited Yosemite National Park (California), was thought to be associated with rodent infestation in cabin insulation

  • Disease develops following inhalation of aerosolized viruses from rodent faeces, urine, or saliva and typically affects previously well young adults

  • Common presenting symptoms are fever, chills, cough, myalgia, and GI symptoms such as vomiting and abdominal pain. Breathlessness occurs later in the disease course and is often quickly followed by respiratory failure and the development of ARDS. Shock may occur and is associated with a poor prognosis

  • Laboratory testing classically reveals neutrophilia, thrombocytopenia, elevated LDH, and sometimes renal impairment and mildly abnormal LFTs. Leucocytosis and immunoblasts in peripheral blood are associated with severe disease

  • CXR typically shows initially bilateral basal infiltrates that progress to involve all regions of the lung; a minority are normal

  • Diagnosis may be confirmed using serology, PCR for the virus, or by detection of viral antigen using immunochemistry

  • Treatment is supportive within an ICU, including the use of extracorporeal membrane oxygenation when appropriate. It is unclear if person-to-person transmission occurs, and patients should be in respiratory isolation. IV ribavirin may be administered, although this has not been demonstrated to improve outcome

  • Mortality 10–50%, with death usually occurring within several days of presentation.

Severe acute respiratory syndrome (SARS)

Caused by SARS-coronavirus (SARS-CoV; an enveloped RNA virus).

Epidemiology

Rapidly progressive acute respiratory illness, first recognized in November 2002 in the Guangdong province of China. By late February 2003, it had spread internationally, with 792 cases reported. First outbreak mainly affected health care workers and contacts. Disease spread to Hong Kong via a Guangdong province physician, who infected individuals in a Hong Kong hotel lift. Spread to Singapore, Thailand, Vietnam, and Canada via travellers. By July 2003, the worldwide epidemic had ended. There were a few cases in 2004, mostly laboratory-related, and no further cases thereafter.

A total of 8, 098 cases were reported to the WHO by August 2003, with 774 deaths, giving a case fatality rate of 9.5%. The fatality rate for those aged ≥60 was 43%. Twenty-nine countries on all five continents were affected; 83% of the worldwide cases were in China and Hong Kong. No deaths occurred in the USA or the UK; 41 deaths (of 251 cases) were in Canada.

Case definition

WHO defined criteria for those presenting with the disease after July 2004 (Respiratory infection—viral http://www.who.int/csr/sars/en):

  • Fever >38°C, plus

  • One or more symptom of lower respiratory tract illness (cough, difficulty breathing, SOB), plus

  • Radiographic evidence of lung infiltrate, consistent with pneumonia or ARDS, or autopsy findings consistent with the pathology of pneumonia or ARDS without identifiable cause, plus

  • No alternative diagnosis to explain the illness.

Laboratory case definition

  • A person with symptoms or signs suggestive of SARS, plus

  • Positive laboratory findings for SARS-CoV, based on one or more of:

    • PCR positive for SARS-CoV for two separate samples

    • Seroconversion by ELISA or immunofluorescence assay

    • Virus isolation.

Pathophysiology

A previously undescribed coronavirus (SARS-CoV) is the causal agent. It is thought that animals, possibly palm civets (similar to cats) or bats, act as the main reservoir.

SARS is mostly spread by large droplets and person-to-person contact. There have been no reports of foodborne or waterborne transmission. However, SARS-CoV is shed in large quantities in stool, and profuse watery diarrhoea is a common symptom.

Lung post-mortem studies show diffuse alveolar damage, 2° bacterial pneumonia, and interstitial giant cell and macrophage infiltration. Pathological findings similar to those of bronchiolitis obliterans are recognized. There are no specific diagnostic features.

Incubation period

is 2–10 days prior to the onset of the first symptom, which is typically fever.

Clinical features

A two-stage illness, commencing with a prodrome of fever (>38°C), with or without rigors, with non-specific systemic symptoms, e.g. malaise, headache, and myalgia.

The respiratory stage of the illness starts 3–7 days after the prodromal phase, with dry cough and breathlessness. Progression to respiratory failure needing ventilation is well recognized. Up to 70% of patients develop large-volume watery diarrhoea without blood or mucus.

Destruction of lung tissue is thought to result from an excessive immune response to the virus, rather than from the direct effects of virus replication. Peak viral load is at day 12–14 of infection, with virus shed not only in respiratory secretions, but in faeces and other body fluids.

Retrospectively devised, but non-validated, scoring systems show that the presence of cough, myalgia, diarrhoea, and rhinorrhoea or sore throat are 100% sensitive and 76% specific at identifying a patient with SARS.

Children experience a milder form of the disease, with a low death rate.

Investigations

  • Blood tests:

    • White blood count is normal or reduced; low lymphocyte count is common. Leucopenia and thrombocytopenia also recognized

    • Raised CK and ALT. Raised LDH is associated with a poorer outcome

  • CXR—ranges from normal to diffuse bilateral interstitial infiltrate. Areas of focal consolidation, initially peripherally and lower zone in distribution, are also described. Cavitation, hilar lymphadenopathy, and pleural effusion are uncommon at presentation

  • CT—interstitial infiltrate, ground-glass opacities, and interlobular septal thickening in those with a normal CXR. Spontaneous pneumothorax, pneumomediastinum, subpleural fibrosis, and/or cystic changes can occur in later stages

  • SARS-CoV can be detected by RT-PCR (sensitivity 70%, dependent on specimen type and duration of illness). Useful specimens include nasopharyngeal aspirate, throat swab, urine, and faeces. An initial positive result on PCR must be confirmed by another clinical sample. Serology is sensitive, but seroconversion takes ~20 days.

Treatment

There is no specific treatment for SARS, other than general supportive care. Ribavirin has been used but no clear benefit and toxicities common. Lopinavir-ritonavir may have some activity, but evidence of benefit is lacking.

Hospital admission

Nosocomial transmission of SARS-CoV has been a striking feature in most outbreaks. Infected and suspected cases should be managed in negative pressure side rooms. Full protective clothing, including protective eye wear and face masks, is recommended for all visitors and health care workers. Aerosol-generating procedures (endotracheal intubation, nebulization, bronchoscopy) may amplify transmission.

Prognosis

Older age is associated with a poorer outcome. Diabetes and other comorbid illness are independent risk factors for death.

Middle East respiratory syndrome (MERS)

  • Caused by the novel MERS-coronavirus (MERS-CoV), an enveloped RNA virus first reported in Saudi Arabia in September 2012

  • Closely related to bat coronaviruses

  • 53 cases reported as of early June 2013, predominantly in Middle East countries (particularly Saudi Arabia) and in travellers returning from the Middle East

  • Most patients are severely ill with pneumonia and ARDS, and many have acute kidney injury

  • Diarrhoea, DIC, and pericarditis also seen

  • Mortality >50%.

Diagnosis

  • Using RT-PCR to detect MERS-CoV in respiratory samples (e.g. nasopharygeal fluid, sputum, or BAL fluid)

  • Testing recommended by WHO for the following:

    • People with acute respiratory infection requiring admission and any of:

      • Disease occurring as part of a cluster occurring within 10 days, unless another aetiology found

      • Disease occurring in a health care worker working in an environment where patients with severe acute respiratory infections are cared for, unless another aetiology found

      • Disease occurring within 10 days of travel to the Middle East, unless another aetiology found

      • Disease follows an unexpectedly severe course despite appropriate treatment

      • People with acute respiratory illness of any severity who had exposure to a probable case of MERS-CoV within 10 days

      • Patients requiring mechanical ventilation in countries where MERS-CoV has been detected.

Treatment

Supportive. Antiviral agents are not currently recommended. Infection control precautions are essential.

Further information

Zaki AM et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012;367:1814–20.Find this resource:

WHO website. Respiratory infection—viral http://www.who.int/csr/disease/coronavirus_infections/en/.