Emerging infectious diseases are often caused by respiratory viruses, which play important roles in respiratory tract infections. They can develop ranging from a common cold to serious respiratory diseases.

Respiratory viruses are a major cause of pediatric morbidity and mortality worldwide. In the last 15 years, molecular detection and sequencing have made it possible to increase the identification of pathogens for common respiratory diseases, as well as the identification of pathogens during pandemics. 

Main respiratory diseases

According to the Forum of International Respiratory Societies, at least two billion people in the world are exposed to toxic smoke from biomass fuel; and more than two billion inhale pollutants and are exposed to tobacco smoke, resulting in a huge burden on global health, in which five respiratory diseases are among the most common causes of death worldwide:

• Chronic obstructive pulmonary disease (COPD): respiratory diseases that block the air flow and make breathing difficult, such as emphysema and chronic bronchitis. Approximately 65 million people suffer from the disease, and about three million die each year, being the third leading cause of death worldwide.
• Lung cancer: it is the most common lethal neoplasm in the world. In 2018, about 2.09 million cases and 1.76 million deaths were registered, according to WHO data. 
• Tuberculosis: an infectious disease transmitted from person to person through the air that mainly affects the lungs. According to the World Health Organization (WHO), there are about 9 million cases of the disease and 2 million deaths per year. 
• Asthma: inflammation of the bronchi that affects about 334 million people worldwide. Despite manifesting itself in all age groups, it is the most common chronic disease in childhood, affecting 14% of children.
• Acute respiratory tract infections: respiratory tract infections are one of the main causes of morbidity and mortality worldwide, with approximately 3 to 5 million severe cases per year, being more frequent in the beginning of fall and winter.

Several new respiratory viruses have emerged, including the influenza A virus (also known as H1N1), the avian influenza A(H7N9) and A(H5N6), the coronavirus responsible for the Middle East Respiratory Syndrome (MERS), and more recently the new coronavirus (Sars-CoV-2) that causes the current COVID-19 pandemic, responsible for more than two million deaths worldwide, so far. Find out more about the new coronavirus in our article “COVID-19 tests: Everything you need to know”.

Main respiratory viruses:

The viruses most often involved in respiratory infections are the rhinovirus, respiratory syncytial virus (RSV), coronavirus, adenovirus, parainfluenza and influenza. All of these viruses share the ability to transmit from person to person, and their transmissibility is influenced by the environment where the pathogen and the host are found.

Learn about viruses related to respiratory tract infections and associated clinical conditions below:

Influenza virus (flu):

Influenza is a respiratory infection caused by the influenza virus (Myxovirus influenzae) with significant rates of morbidity and mortality worldwide. Influenza viruses are classified as type A, B, and C, through their nucleoproteins and matrix proteins.

Influenza, or the flu, usually causes mild respiratory problems, such as:

• cough; 
• fever; 
• myalgia;
• chills or sweats;
• malaise.

Symptoms can persist for two to eight days. 

Gastrointestinal symptoms such as vomiting and diarrhea can occur in children.

A minority of patients, especially the elderly, will experience severe disease due to viral or bacterial pneumonia.

Types A and B influenza

Types A and B of the influenza virus are responsible for seasonal epidemics, with influenza A virus (H1N1pdm09 and H3N2) infection being characteristic of the abrupt onset of:

• fever;
• cough;
• chills or sweats; 
• myalgia and malaise. 

Subtypes: 

Subtype H1N1 emerged from a quadruple grouping of two porcine viruses, an avian virus and a human virus, causing the virus pandemic in 2009. In which symptoms are usually mild with nausea, vomiting and diarrhea, but can worsen causing pneumonia or respiratory failure.

The incidence and mortality of swine flu or H1N1 infection is higher among young adults and lower in elderly patients compared to those of seasonal influenza, most likely because the youngest have not previously been exposed to other similar influenza viruses. 

The name of the virus was standardized for influenza A (H1N1)pdm09 in order to denote the pandemic and to distinguish the virus from the seasonal H1N1 strains and the pandemic H1N1 strain. 

Since 2011, outbreaks of the H3N2 subtype of swine origin have been reported predominantly in children. In addition, the H5N1 influenza or avian influenza virus has become a global concern. 

Prevention:

As a way of preventing influenza viruses, the annual flu vaccination is recommended for all individuals. Vaccination efforts should primarily target people at higher risk for complicated or severe influenza (the elderly and the immunosuppressed individuals) and those who care for or live with high-risk individuals, including healthcare professionals. Current vaccines against seasonal influenza are also effective against the A (H1N1)pdm09 virus.

Parainfluenza

The parainfluenza virus (PIV) is an RNA virus of the Paramyxoviridae family, classified into four serotypes (PIV-1, PIV-2, PIV-3, and PIV-4), which cause several respiratory diseases ranging from a common cold to an influenza-like illness or pneumonia, being a known cause of infection in pediatric and immunocompromised patients, and has recently been recognized as a relevant pathogen in hospitalized adults, with infection rates between 2 and 11%. 

They are the second most common cause of lower respiratory tract infection in children.

Symptoms include:

• cough; 
• coryza/runny nose; 
• sore throat; 
• asthma;
• chronic obstructive pulmonary disease (COPD);
• heart failure;
• pneumonia;
• Croup (acute obstruction of the larynx) – as the most common severe manifestation. 

There is evidence to suggest that PIV can result in mild, asymptomatic recurrent infections in adult populations, with long periods of asymptomatic viral elimination (> 8 months).

Serotypes 1 and 2 tend to cause epidemics in the fall, with each serotype occurring in alternate years. Serotype 3 is usually endemic and infects most children under one year of age and can cause pneumonia and bronchiolitis; while serotype 4 has antigenic cross-reactivity with the mumps virus.

Human respiratory syncytial virus

The respiratory syncytial virus (RSV) is an enveloped RNA pneumovirus belonging to the Paramyxoviridae family. It is the most important viral agent that causes severe respiratory diseases in babies and children worldwide. 

RSV infections are responsible for one third of deaths related to acute lower respiratory infection in babies under one year of age and are particularly problematic in premature babies, as well as in children with heart problems and breathing problems. The virus also causes serious illness in the elderly population.

About 40 to 60% of children are infected with RSV in the first year of life, and more than 95% of children, at 2 years of age, have had or will have at least one RSV infection. 

In addition, RSV infection is an important cause of morbidity in adults, particularly in the elderly and immunocompromised individuals.

Transmission:

RSV is transmitted by contact with the infected person’s oral or nasal secretions when coughing, sneezing or speaking and, indirectly, by contact with contaminated surfaces and objects and causes recurrent infections throughout life. An RSV infection causes innate and adaptive immune responses, but immunity against the virus is not long-lasting. The transmission period starts two days before symptoms appear and ends only when the infection is under control.

The respiratory syncytial virus has a seasonal circulation, with a higher detection rate in late fall and early spring. In tropical regions it can be detected all year round.

The main associated symptoms can range from mild symptoms (in people in good health conditions) such as:

• coryza/runny nose; 
• sneezing; 
• dry cough; 
• fever; 
• sore throat; 
• headache; 
• otitis;
• lower respiratory tract infection. 

Even more serious conditions like acute bronchiolitis (inflammation of the bronchioles) and pneumonia.  

Involvement of the lower respiratory tract occurs in about 15–50% of babies and children with primary infection, hospitalization is necessary in 1–3% of cases with babies between 2 and 6 months of age, who are at greater risk.

The acute phase of this infection is often followed by episodes of wheezing that are repeated for months or years and usually lead to a diagnosis of asthma.

Treatment consists of bronchodilators and mucolytic agents, while young pediatric patients at high risk also receive prophylactic treatment with monoclonal antibodies (Palivizumab). 

Metapneumovirus

Human metapneumovirus (HMPV) is a significant cause of diseases of the upper and lower respiratory tract in children and adults. It is an RNA virus that belongs to the Paramyxoviridae family, which also includes the respiratory syncytial virus (RSV) and parainfluenza viruses.

The metapneumovirus generally causes upper respiratory tract infection and flu-like diseases, but it is also associated with lower respiratory tract infections, such as wheezing bronchitis, bronchitis, bronchiolitis and pneumonia, in small children, the elderly and immunocompromised patients. 

Symptoms usually include:

• coryza/runny nose; 
• fever; 
• productive wheezing cough; 
• rhinorrhea; 
• sore throat; 
• dyspnea; 
• vomiting;
• diarrhea;
• migraine;
• exacerbation of asthma can also occur.

In babies under six months of age, the first symptom may be a period of interrupted breathing. Some small babies develop severe respiratory distress. In healthy adults and older children, the disease is usually mild and can manifest itself only in the form of a common cold. Most children do not need to be admitted to the hospital. 

Diagnosis and transmission: 

When necessary, samples of nasal secretion are analyzed with a rapid examination of antigens, and the polymerase chain reaction (PCR) technique helps to identify the virus.

Transmission occurs through direct contact with the infected person or close to infected secretions. 

Home treatment consists mainly of symptomatic relief. 

Seroprevalence studies show that primary infection occurs before the age of 5 and that people are reinfected throughout life. The four subgroups of HMPV occur with year-to-year variability. 

Humoral immunity plays an important role in HMPV infection, and the study of HMPV antibodies provides important information, including HMPV seroprevalence, cross-serological protection among HMPV subgroups and strategies for prophylaxis and therapy using monoclonal antibodies (mAbs). Widely neutralizing monoclonal antibodies have significant clinical implications for the prophylaxis and treatment of hosts at high risk .

Adenovirus

Adenoviruses (AdVs) are DNA viruses that usually cause mild infections involving the upper or lower respiratory tract and the gastrointestinal tract. Adenovirus infections are more common in young children, due to a lack of humoral immunity.

There are seven species of human adenovirus (A – G) and approximately 57 different serotypes and the predominant ones detected in association with the disease differ among countries or regions, and may change over time.

Typical symptoms include:

• fever;
• pharyngitis; 
• tonsillitis; 
• cough;
• sore throat; 
• Hemorrhagic cystitis;
• Hepatitis;
• Hemorrhagic cystitis;
• Pancreatitis;
• Nephritis;
• Meningoencephalitis. 

Gastrointestinal symptoms may be present particularly in children, and pneumonia occurs in up to 20% of newborns and babies. 

The severe clinical picture is more likely in immunocompromised patients (transplant recipients, human immunodeficiency virus infection) and develops in 10 to 30% of cases. 

Transmission:

Adenovirus infections are increasingly recognized as causes of severe respiratory disease and can result from exposure to infected individuals (droplet inhalation, conjunctival inoculation) and contaminated objects. 

The incubation period varies from two to 14 days, and the latent AdV can reside in lymphoid tissue, renal parenchyma or other tissues for years; reactivation can occur in severely immunosuppressed patients. 

Rhinovirus

Human rhinoviruses (RVs) are responsible for more than half of flu-like diseases, being the most common cause of upper respiratory tract infection and cost billions of dollars annually in medical appointments and lost days of work and school. 

Approximately 50% of all colds are caused by one of the more than 100 existing rhinovirus serotypes, which are very common during fall and spring and less common during the winter months.

The most common symptoms are:

• pharyngitis followed by sneezing; 
• nasal obstruction and malaise;
• exacerbations of chronic lung disease;
• development of asthma;
• severe bronchiolitis (in babies and children);
• fatal pneumonia (in the elderly and immunocompromised adults). 

Transmission: 

Rhinoviruses are transmitted from person to person via direct contact with large particles in the air. HRV infection begins by intranasal and conjunctival, but not oral inoculation. Scientific studies have shown that the virus is regularly deposited in the hands and introduced into the environment, since it was detected in 40% of the hands of naturally infected volunteers and 6% of objects at home.

Enterovirus

Respiratory enteroviruses (EVs), as well as rhinoviruses (RVs), small RNA viruses, are the main causes of infections of the upper respiratory tract and are among the most frequent infectious agents in humans worldwide. Both belong to the Picornaviridae family and were classified into seven distinct species, being three species of rhinovirus (RV-A to RV-C) and four species of enterovirus (EV-A to EV-D). Despite being from the same family, the characteristics of these viruses are different; the tropism (the ability of a virus to specifically infect certain cells in the body) in RVs is restricted to the upper respiratory tract, except in rare cases, while EVs can infect a wide range of different cells and cause very different clinical conditions. 

EVs diseases vary from:

• febrile illnesses to myopericarditis; 
• poliomyelitis; 
• hand-foot-and-mouth disease; 
• paralysis;
• encephalitis; 
• viral meningitis. 

While other types of enteroviruses are found only in the respiratory tract and cause symptoms similar to those of rhinovirus, mainly EVs of species C and D, and they are consequently called respiratory enteroviruses.

Transmission: 

The transmission of the virus occurs mainly through direct contact or through a contaminated object (fomites), usually with inoculation in the eye or nose by the fingertip. These viruses are able to survive in the hands for several hours, which allows easy transmission from person to person in the absence of proper hand hygiene, especially in the presence of high viral loads. 

Bocavirus

The human bocavirus (HBoV) is a parvovirus, isolated about a decade ago, found in respiratory samples, mainly in children from 6 to 24 months of age with acute respiratory infection, and in stool samples from patients with gastroenteritis. Since then, three additional HBoV subtypes (HBoV1) have been identified in stool samples and named HBoV2, HBoV3, and HBoV4. The virus was detected in other biological samples, such as blood, saliva and urine, as well as in river and sewage water samples.

HBoV mainly affects children aged 6 to 24 months with respiratory symptoms such as:

•  rhinitis;
• pharyngitis; 
• cough;
• dyspnea;
• pneumonia;
• acute otitis media;
• fever;
• nausea;
• vomiting;
• diarrhea; 
• exacerbation of asthma.

HBoV2, like the other subtypes, is found most often in stool samples and is associated with gastroenteritis, as well as possibly HBoV3. More recent studies show that HBoV can be detected specifically in tissues such as duodenum, paranasal sinus mucosa and intestinal biopsies.

The bocavirus enters the  body through the respiratory tract and the bloodstream or by direct ingestion, reaching the gastrointestinal tract. Cases of HBoV infection show a high rate of co-infections with other respiratory pathogens and gastroenteritis such as human rhinovirus, adenovirus, norovirus and rotavirus.

Coronavirus

Coronaviruses are a family of enveloped RNA viruses, classified in the order of Nidovirales. This family of coronaviruses consists of pathogens of various animal and human species, including severe acute respiratory syndrome (SARS-CoV) and the new coronavirus (SARS-CoV-2). Human coronaviruses were only known to cause the common cold, until in 2003, the SARS-CoV coronavirus was responsible for severe acute respiratory syndrome (SARS). 

Coronaviruses cause acute and chronic respiratory, enteric and central nervous system (CNS) diseases in animals and humans. The most common types that infect humans are:

• Alpha coronavirus (229E and NL63): subtype 229E is considered an etiologic agent of the common cold, while subtype NL63 was isolated in children with severe respiratory symptoms, including upper respiratory infection, bronchiolitis and pneumonia, and in immunocompromised adults with infections of the respiratory tract.
• Beta coronavirus (OC43 and HKU1): the OC43 subtype is also considered an etiological agent of the common cold. On the other hand, subtype HKU1 was associated with elderly patients with pneumonia.
• SARS-CoV (causing the Severe Acute Respiratory Syndrome or SARS): discovered in February 2003 when the World Health Organization (WHO) received reports from China about a new respiratory disease outbreak with cases of “atypical pneumonia”. At the end of the epidemic, more than 8,000 cases were reported, with more than 800 deaths worldwide. SARS infection shows a wide clinical presentation, characterized mainly by fever, dyspnea, lymphopenia, and lower respiratory tract infection. Gastrointestinal symptoms and diarrhea are also common. Infected individuals have slightly decreased platelet counts, prolonged coagulation profiles and slightly elevated serum liver enzymes. It has been suggested that airborne droplets from infected patients may be the main route of transmission.

The discovery of the ACE2 enzyme in human cells as a receptor for SARS-CoV (187) demonstrated how SARS-CoV enters host cells and has enabled the molecular elucidation of the cross transmission of SARS-CoV.

• MERS-CoV (which causes the Middle East Respiratory Syndrome or MERS): MERS-CoV is similar to SARS-CoV, which manifests itself as a severe lower respiratory tract infection with extrapulmonary involvement and high mortality rates. The MERS is considered by the global health community as a potential pandemic agent with a high rate of person-to-person transmission and limited effective therapeutic options. The first reports of MERS focused on severe cases with a clinical picture of acute pneumonia with rapid respiratory deterioration and extrapulmonary manifestation. Common symptoms of MERS are nonspecific and include fever, chills, sore throat, dry cough, dyspnea, chest pain, myalgia, headache, and malaise.
• SARS-CoV-2 (which causes COVID-19): the new SARS-COV-2 coronavirus (severe acute respiratory syndrome coronavirus 2) is the virus that causes the disease that became known as Corona Virus Disease (COVID-19) and of the current pandemic. Learn more about SARS-CoV-2 in our article.

Recommendations for the Prevention of Respiratory Viruses

The prevention of respiratory viruses is directly associated with basic hygiene care, such as frequent washing of hands with soap and water, application of hand sanitizer gel before and after coming into contact with infected people, the disinfection of surfaces and objects contaminated by the virus, and an adequate diet. Avoiding crowds in closed places and keeping distance from people who show signs of the disease are important measures to control the spread of viruses.

Diagnosis of respiratory viruses:

The diagnosis of respiratory infections is usually clinical, based on the manifestation of symptoms of a common cold, bronchiolitis, croup or pneumonia, for example, and by local epidemiology. However, advances in molecular methods have facilitated the detection and characterization of groups and strains of the various respiratory viruses, and are needed mainly when specifying the pathogen modifies clinical treatment and to identify and to determine the cause of an outbreak.

What test does Synlab offer for respiratory viruses?

Synlab offers a molecular panel of DNA and RNA respiratory viruses responsible for respiratory diseases, comprising the detection of the following viruses: Influenza A (H1, H3, H1pdm09), Influenza B, Respiratory Syncytial Virus (A/B), Metapneumovirus, Adenovirus (AdV A/B/C/D/E/F), Coronavirus/CoV 229E/NL63/OC43), Enterovirus, Rhinovirus (HRV A/B/C), Bocavirus (HBoV 1/2/3/4), Parainfluenza Virus (PIV 1/2/3/4) in upper respiratory tract samples (nasopharyngeal/oropharyngeal exudate) and lower respiratory tract samples (BAL, sputum and/or BAS) obtained by swab or scraping of the affected site. 

Detection is performed by real-time polymerase chain reaction (qPCR).

Indicated in cases of:

• respiratory disease without knowledge of the causative pathogen, 
• specification of the pathogen is necessary to determine the appropriate treatment,
• choice of specific antiviral,
• epidemiological surveillance and control.

About the SYNLAB Group

The SYNLAB Group is a leader in providing medical diagnostic services in Europe, providing a full range of clinical laboratory analysis services to patients, healthcare professionals, clinics and the pharmaceutical industry. Resulting from the Labco and Synlab merger, the new SYNLAB Group is the undisputed European leader in medical laboratory services.