Respiratory Viruses Feb 7 2024.pptx

Respiratory Viruses Murray’s Basic Medical Microbiology, Chapter 15 February 5, 2024 Dr. Angela Benton Many of the respiratory viruses produce similar symptoms Clinically indistinguishable from each other No antiviral treatment for many of these viruses Exception  influenza Upper respiratory and lo...

Respiratory Viruses Murray’s Basic Medical Microbiology, Chapter 15 February 5, 2024 Dr. Angela Benton Many of the respiratory viruses produce similar symptoms Clinically indistinguishable from each other No antiviral treatment for many of these viruses Exception  influenza Upper respiratory and lower respiratory tract can be affected Simultaneously or individually Rhinoviruses + sense, ss Coronaviruses RNA Influenza viruses Parainfluenza virus - sense, ss Respiratory syncytial virusRNA Human metapneumovirus Adenovirus dsDNA + sense, ssRNA virus 1. Virus binds to cell receptor 2. Endocytosis 3. Genome is used as mRNA for protein synthesis One large polyprotein is made 4. Polyprotein is cleaved 5. Macromolecular synthesis proceeds In a replication vesicle made by the virus Polymerase make a (-)strand template from the genome  replication 6. Structural proteins make capsid, genome is inserted, and virions are released (-) sense, ssRNA virus 1. Virus binds to cell receptor 2. Endocytosis 3. mRNA is produced by viral polymerase 4. Proteins are translated 5. Genome is replicated from the (+) RNA template 6. Assembly of the nucleocapsid 7. Virus buds from the cell Rhinoviruses + sense, ssRNA virus Nonenveloped – more stable/resistant to degradation Worldwide distribution – infects both children and adults Most common cause of acute upper respiratory viral infections Infections occur throughout the year Peak in fall/spring Multiple serotypes + short lived immunity = recurrent disease Rhinoviruses Transmission is most common with large droplets Cough/sneeze  hands contaminated  transfer to nose or eyes Transmission is most efficient when symptoms are more severe Greater symptoms = more infectious virions in secretions Symptoms are caused by infection of respiratory ciliated epithelial cells Stimulates cellular inflammatory response Clinical Disease – Rhinovirus Primarily an upper respiratory tract infection Initiated with sore, “scratchy” throat Followed with rhinorrhea and nasal obstruction Cough, sneezing, headache, and low-grade fever also develops Symptoms can persist for ~1 week Can last longer Diagnosis and Treatment – Rhinovirus Diagnosis Definitive diagnosis CANNOT be made from clinical parameters Nucleic acid amplification test for definitive diagnosis Treatment No specific antiviral therapy No vaccines Rest/hydration Coronaviruses Enveloped, + sense, ssRNA virus Responsible for ~15% of common colds Infections are primarily in winter and spring Common cold coronaviruses have worldwide distribution SARS-CoV-1 and MERS-CoV outbreaks were more restricted geographically SARS-CoV-2 had global spread Replicate in epithelial cells of the nasopharynx Stimulates production of cytokines and chemokines  induces “cold” symptoms Coronaviruses SARS-CoV Severe acute respiratory syndrome – Coronavirus Epidemic outbreak (2002) – lasted 18 months Person to person spread occurred readily Emerged in China; Rapidly spread from Hong Kong to Vietnam to Singapore Healthcare workers caring for patients Relatively high mortality rate ~10% of patients Worse in elderly and patients with underlying pulmonary disease Coronaviruses MERS-CoV Middle East Respiratory Syndrome – Coronavirus Epidemic outbreak (2012) Intermittently spread person to person Seen in people who have close contact with camels – reservoir Saudi Arabia  other middle eastern countries via travelers Mortality rate ~35% More likely to lead to respiratory and multiorgan failure Coronavirus Stable envelop structure Spike protein binds to ACE-2 receptor Mucous epithelium of upper respiratory tract, lung and GI tract Vascular epithelium Neurons Lymphocytes Children have less ACE-2 expression than adults Also binds to CD147 Expressed on epithelium and immune cells SARS-CoV-2 Pathogenesis Initiates infection of the upper respiratory tract Later moves to lung Evades initiation of type 1 and 3 interferons Allows for quicker spread to surrounding cells with less symptoms Cytolysis triggers DAMPs Activates acute phase response from macrophages Greater inflammation and potential for cytokine storm Clinical Disease – Coronaviruses Common cold strains ~2 day incubation period Peak symptoms 3-to-4 days after exposure Sore throat, rhinorrhea, cough, headache Recovery is uneventful Clinical Disease – SARS-CoV-1 and SARS-CoV-2 Typically present with fever, headache, myalgia Followed by a nonproductive cough Hallmark characteristic of loss of smell/taste Progression to severe pulmonary disease Most likely in older patients or those with co-morbidities Diabetes, cardiac disease, hepatitis, chronic pulmonary disease Diagnosis – Coronaviruses Diagnosis is most commonly done by PCR SARS-CoV-2 diagnosis can be done by rapid, point-ofcare immunoassays Culturing the viruses is only done in public health laboratories Treatment – Coronaviruses Remdesivir and ritonavir-nirmatrelvir – SARS-CoV-2 Vaccines are only available for SARS-CoV-2 Rigorous infection control practices to prevent spread of SARS-CoV-1 and MERS-CoV Masks, handwashing, social distancing, etc Influenza Viruses Enveloped, (-) sense, ssRNA virus Three types of virus – A, B, C Strains are identified by surface proteins Hemagglutinin (HA) and neuraminidase (NA) Worldwide distribution Infections primarily occur in the cold months Transmission occurs via respiratory droplets Talking, breathing, coughing, sneezing Pandemic Influenza Outbreaks Pandemic strains of influenza – influenza type A Spanish flu; bird flu; swine flu Hemagglutinin can undergo minor or major changes Minor – antigenic drift Major – antigenic shift  pandemics Changes in HA allow for changes in receptor specificity and antigenicity zoonosis Influenza Virus infects ciliated columnar epithelial cells of the trachea and bronchials HA facilitates attachment to sialic acid on epithelial cell surface Causes aggregation of RBC Neutralizing antibodies are made against HA NA cleaves sialic acid Prevents clumping of the HA and virions Facilitates the release of virus from infected cells Clinical Disease – Influenza Incubation of 1-to-4 days Brief prodromal period of malaise and headache Lasts a few hours Prodromal period is followed by an abrupt and intense onset of symptoms Nonproductive cough, high fever, chills, appetite loss, weakness, fatigue, sore throat Fever persist for ~3-to-8 days Recovery is complete within 7-to-10 days Complications from Influenza Can directly cause pneumonia More commonly promotes a secondary bacterial superinfection Can progress to a potentially fatal pneumonia Hypoxia and bilateral pneumonia can result from alveoli infection Inflammatory response can lead to myocarditis, myositis, encephalopathy Reye syndrome Acute encephalitis that affects children Increased risk if child is given aspirin 40% mortality rate Diagnosis and Treatment – Influenza Diagnosis Immunoassays and NAATs Specific diagnosis is important for guiding antiviral therapy Treatment Influenza A and B – neuraminidase inhibitors Zanamivir, oseltamivir, peramivir Must be taken early in infection Vaccination for prevention/less severe disease Parainfluenza Viruses Enveloped, (-) sense, ssRNA virus Four major serotypes Most significant cause of “croup” in children Severe lower respiratory tract disease in immunocompromised patients Worldwide distribution PIV-1 and PIV-2 cause outbreaks in the fall PIV-3 and PIV-4 cause outbreaks in the spring Parainfluenza Virus Preferentially infect ciliated epithelial cells of the upper respiratory tracts Rarely causes viremia ~25% of cases  virus moves to lower respiratory tract Replicates rapidly Can cause giant cell formation and cell lysis Person to person transmission Respiratory droplets and contact with contaminated surfaces Clinical Disease – Parainfluenza Virus Most pediatric infections are limited to upper respiratory tract Symptoms developing about 1 day after exposure persisting for a week or more involvement of the sinuses/middle ear occurs in ~50% of children infected PIV-1 and PIV-2 associated with laryngotracheobronchitis (croup) initial development of fever, rhinorrhea, and pharyngitis progressing to barking cough associated with stridor difficulty in breathing PIV-1 disease is generally more severe than the PIV-2 disease Clinical Disease – Parainfluenza Virus PIV-3 disease is more commonly associated with pneumonia and bronchiolitis in children PIV-4 primarily causes mild upper respiratory infections PIV infections in adults are generally asymptomatic or mild upper respiratory infections except in immunocompromised patients – severe lower respiratory tract disease can develop Diagnosis and Treatment – Parainfluenza Virus Diagnosis NAATs Treatment No specific antiviral treatment Croup is managed symptomatically with glucocorticoids and nebulized epinephrine Vaccine is not available Respiratory Syncytial Virus Enveloped, (-) sense ssRNA virus 2 major antigenic groups – A and B Both groups circulate in population simultaneously Worldwide distribution Infects both children and adults More severe in infants Responsible for the majority of bronchiolitis ~50% of hospitalization for pneumonia Majority of otitis media Children RSV Infects ciliated columnar epithelial cells of the lower airways Also infects pneumocytes in the lungs Person-to-person spread Respiratory droplets or contact with contaminated surfaces Infections occur annually from late fall through early spring May extend through the year in warmer climates (FLORIDA) Initial infections in early life Milder recurrent infections throughout life Clinical Disease – RSV Infection in infants primarily involves the lower respiratory tract 2- to 5-day incubation period – initially presents as an upper respiratory tract infection with nasal congestion and cough Presents as bronchiolitis Pneumonia can develop Croup occurs less commonly Otitis media is associated with pediatric disease co-infections with bacterial pathogens are responsible for more severe otitis Clinical Disease – RSV Adult disease is primarily mild Severe lower respiratory disease is seen in the elderly, immunocompromised adults Also seen in patients with underlying cardiopulmonary disease chronic obstructive pulmonary disease, congestive heart failure Diagnosis and Treatment – RSV Diagnosis Point of care rapid test for infants NAATs Treatment Mild infections are treated symptomatically Bronchiolitis is generally managed with bronchodilators and corticosteroids Ribavirin is approved for the treatment of hospitalized infants with lower respiratory tract disease Vaccine available now for at-risk infants Human Metapneumovirus Enveloped, (-) sense, ssRNA virus Very closely related to RSV Two genotypes with multiple subgroups Diversity of the surface glycoproteins results in many novel virus strains Worldwide distribution Infections are most common in the winter and spring Same as RSV/influenza HMV Infection of bronchial epithelial cells results in prolonged inflammatory response Ranges from mild URI to bronchitis and severe pneumonia Immunity is incomplete Reinfections can occur throughout life Primary infection occurs by age 5 Severity of infections are directly related to co-infections with RSV or S. pneumoniae Clinical Disease – HMV Infections in children characterized by fever, cough, wheezing, and rhinorrhea conjunctivitis, pharyngitis, laryngitis, and otitis may occur involvement of the bronchial airways and lungs may develop Adult disease is similar to that in children lower respiratory complications more common in patients with underlying respiratory disease or immunosuppression Diagnosis and Treatment – HMV Diagnosis NAATs Treatment No specific antiviral treatment Symptomatic treatment Rest/hydration No vaccine Adenovirus Nonenveloped DNA virus Commonly associated with people in “closed environments” Children in schools, prisoners, and military barracks Cold-like symptoms with exudative pharyngitis that is clinically and symptomatically indistinguishable GAS Can also cause a pertussis like syndrome and pneumonia Questions?