Influenza & Other Respiratory Viruses Flashcards
2 clinically relevant influenza viruses
- type A:
-potentially severe illness
-epidemics and pandemics
-rapidly changing - type B:
-usually less severe illness
-epidemics
-genetically more stable
influenza virus - structure & virulence factors
*negative sense, single-stranded, enveloped RNA virus belonging to the Orthomyxoviridae family
*virulence proteins:
-hemagglutinin (H1-H18)
-neuraminidase (N1-N11)
-M2 protein
hemagglutinin
*important virulence factor of the influenza virus
*binds to sialic acid residues on respiratory epithelial cell surface glycoproteins
*immunity can be measured by detecting levels of neutralizing antibody to hemagglutinin
neuraminidase
*important virulence factor of the influenza virus
degrades the mucus barrier** of the respiratory epithelial cells
**facilitates release of virions after the virus has matured within host cells by cleaving sialic acid residues
influenza A subtypes
*various subtypes, grouped according to variations in HA and NA
*6 HA subtypes (importantly: H1, H2, and H3) and 5 NA subtypes (importantly: N1, N2) have infected humans
*hence, H1N1 and other types of influenza
influenza B subtypes
*influenza B only has one form of HA and one form of NA (so we can just call it influenza B)
antigenic drift
*SMALL annual drift in minor determinants of H and N proteins
*occurs through a series of mutations, substitutions, or deletions in amino acids constituting the hemagglutinin or neuraminidase surface antigens
*occurs only after a partial viral strain has become established in humans
*represents an adaptation to the development of host antibodies
*newly developed antigenic strains prevail for a period of 2-5 years, only to be replaced by the next emerging strain
*occurs in both influenza A and B
influenza EPIDEMICS are a result of antigenic drift or antigenic shift?
antigenic DRIFT
antigenic shift
*LARGE shifts in H or N subtypes by RECOMBINATION
*occurs when type A influenza virus with a novel hemagglutinin or neuraminidase moves into humans from OTHER HOST SPECIES
*shifts occur less frequently than drifts
*only occurs in influenza A
*more dramatic impact due to global immunologic susceptibility = PANDMEIC
*ex. influenza pandemic of 2009 was caused by genetic reassortment between human and swine influenza A viruses
influenza PANDEMICS are a result of antigenic drift or antigenic shift?
antigenic SHIFT
predominant strains of circulating influenzas
*2 strains of type A (~80%) and 2 strains of type B (~20%)
*H3N2 (type A)
*H1N1 (type A)
*B/Yamagata lineage (type B)
*B/Victoria lineage (type B)
influenza transmission
*highly infectious
*transmitted by respiratory droplets:
-sneezing, coughing, talking
-contact with infected surfaces, then touching mouth, eyes, nose
*period of contagiousness:
-1 day before symptoms develop
-5 to 7 days after becoming sick
*incubation period: average 2 days
diagnosis of influenza
*rapid molecular assay - run on nasopharyngeal swab to detect influenza virus nucleic acids (15-30 minutes)
*PCR can be performed on respiratory samples (1-8 hour turn-around time)
influenza - clinical manifestations
*febrile respiratory illness: sudden onset fever, myalgias, fatigue, cough
*mostly self-limited
risk factors for hospitalization due to influenza
*elderly
*children < 2 yo
*pregnant women
*persons with comorbidities (lung disease, heart disease, neurologic disease, renal disease, obesity)
influenza clinical syndromes & complications: VIRAL PNEUMONIA
*rapid progression of fever, cough, dyspnea, hypoxia
*acute respiratory distress syndrome (ARDS) can result
*high mortality rate
*highest risk = heart disease, pregnancy
2 organisms important for post-influenza bacterial pneumonia
- strep pneumo
- staph aureus!
influenza clinical syndromes & complications: SECONDARY BACTERIAL PNEUMONIA
*characterized by typical influenza, recovery, then relapse of respiratory symptoms
*fever, cough productive of purulent sputum, lobar consolidation
*more common than viral pneumonia
*highest risk: elderly, underlying lung disease
*causative organisms:
1. strep pneumo
2. staph aureus
3. group A strep
pathogenesis of secondary bacterial pneumonia after influenza virus
*destroyed/damaged physical barriers of the respiratory mucosa
*immune system dysfunction (increased glucocorticoid levels)
*increased bacterial adherence (neuraminidase-mediated)
influenza clinical syndromes & complications: MYOSITIS & RHABDOMYOLYSIS
*more common in children
*muscle tenderness, especially in the legs
*markedly elevated serum creatinine phosphokinase (CPK) levels
influenza clinical syndromes & complications: CNS involvement - Guillain Barre Syndrome
*ascending, progressive, symmetric muscle weakness
*absent or depressed deep tendon reflexes
influenza clinical syndromes & complications: CNS involvement - Reye syndrome
*rapidly progressive encephalopathy and hepatic dysfunction in children
*aspirin use is a risk factor
*peak in 1980s, less common now
influenza clinical syndromes & complications: MYOCARDITIS & PERICARDITIS
*not uncommon
*many people will present in ICU with this
important antiviral agent used for influenza
OSELTAMIVIR
oseltamivir - uses and MOA
*antiviral medication used for type A and type B influenza treatment/prevention
*neuraminidase inhibitor (blocks the viral neuraminidase enzyme)
*reduces symptom duration by 1-2 days
*reduces the risk of hospitalization
*reduces risk of pneumonia by 55%
*should be prescribed within the FIRST 48 HOURS OF SYMPTOM ONSET, but still benefit for seriously ill patients
*can be used for prophylaxis in conjunction with influenza vaccine
influenza vaccination
*quadrivalent vaccine:
-contains antigens from 4 strains of influenza viruses
-two influenza A strains (H3N2 & H1N1) and two influenza B strains
*everyone over the age of 6 months should get vaccinated; prioritize elderly, children/adolescents, high risk comorbidity, and health-care workers
*Oct-Nov is peak vaccination season
*takes about 2 weeks to be fully effective
influenza vaccine efficacy
*efficacy 70-90%, depending on circulating strains & host population
*reduces risk of respiratory illness, pneumonia, hospitalization, death
*cost effective
adenovirus - overview
*DNA virus
*10% of respiratory infections
*outbreaks among children, young adults, military
adenovirus - clinical manifestations, diagnosis, treatment
*fever, pharyngitis
*conjunctivitis
*pneumonia
*myocarditis
*hemorrhagic cystitis
*hepatitis
*diagnosis: PCR
*tx: supportive
SARS-CoV-2 - overview
*enveloped, RNA virus in the coronaviridae family
*transmitted by aerosols, droplets
*adapts with genetic evolution and developing mutations
*disease: COVID-19
SARS-CoV-2 - clinical manifestations
*clinical manifestations vary with variants:
-fever, chills, cough, SOB, sore throat, congestion, new loss of taste/smell, fatigue, muscle or body aches, headache, nausea, vomiting, diarrhea
*severe manifestations:
-respiratory failure
-ARDS
-septic shock
-myocarditis/pericarditis
-coagulopathies
-CVA
-MI
-kidney injury/failure
SARS-CoV-2 - antivirals
*remdesivir (inhibits RNA polymerase)
*nirmatrelvir with ritonavir (inhibits viral protease)
SARS-CoV-2 - binding mechanism
*receptor-binding domain (RBD) of spike protein binds to ACE2
SARS-CoV-2 - immune modulators
*suppress hyperinflammation due to COVID-19 (ex. corticosteroids, IL-6 inhibitors, JAK inhibitors)
SARS-CoV-2 - monoclonal antibodies
*mAbs block entry of SARS-CoV-2 into human cells and neutralize the virus
SARS-CoV-2 - mRNA vaccines
*mRNA for SARS-CoV-2 spike protein
*98% effective in preventing severe disease
*induces human cells to develop antibodies against the spike protein
*ADEs: injection site pain, redness, swelling, fatigue, headaches, myalgias
SARS-CoV-2 - protein subunit (adjuvant) vaccines
*spike protein fragments
*95-99% effective in preventing moderate to severe disease
paramyxoviruses
*enveloped, RNA viruses
*RSV, parainfluenza (croup), measles, mumps
respiratory syncytial virus (RSV)
*enveloped, RNA virus in paramyxovirus family
*clinical manifestations: upper respiratory illness (cough, fever, wheezing, apnea), bronchiolitis, pneumonia
*highest risk: infants < 6 months, premature infants, age < 2 with chronic medical conditions
*diagnosis: antigen or PCR
*prevention: RSV vaccine, Nirsevimab
measles
*enveloped, RNA virus in paramyxovirus family
*acute, highly contagious viral respiratory illness
*clinical syndrome: fever, malaise, 3 C’s (cough, coryza, conjunctivitis), Koplik spots, maculopapular rash
*complications: otitis media, pneumonia, death, acute encephalitis, subacute sclerosing pancencephalitis
*prevention: MMR vaccine (live, attenuated vaccine)
