Influenza & Other Respiratory Viruses

Question 1

2 clinically relevant influenza viruses

Answer 1

1. type A:
   -potentially severe illness
   -epidemics and pandemics
   -rapidly changing
2. type B:
   -usually less severe illness
   -epidemics
   -genetically more stable

Question 2

influenza virus - structure & virulence factors

Answer 2

*negative sense, single-stranded, enveloped RNA virus belonging to the Orthomyxoviridae family
*virulence proteins:
-hemagglutinin (H1-H18)
-neuraminidase (N1-N11)
-M2 protein

Question 3

hemagglutinin

Answer 3

*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

Question 4

neuraminidase

Answer 4

*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

Question 5

influenza A subtypes

Answer 5

*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

Question 6

influenza B subtypes

Answer 6

*influenza B only has one form of HA and one form of NA (so we can just call it influenza B)

Question 7

antigenic drift

Answer 7

*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

Question 8

influenza EPIDEMICS are a result of antigenic drift or antigenic shift?

Answer 8

antigenic DRIFT

Question 9

antigenic shift

Answer 9

*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

Question 10

influenza PANDEMICS are a result of antigenic drift or antigenic shift?

Answer 10

antigenic SHIFT

Question 11

predominant strains of circulating influenzas

Answer 11

*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)

Question 12

influenza transmission

Answer 12

*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

Question 13

diagnosis of influenza

Answer 13

*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)

Question 14

influenza - clinical manifestations

Answer 14

*febrile respiratory illness: sudden onset fever, myalgias, fatigue, cough
*mostly self-limited

Question 15

risk factors for hospitalization due to influenza

Answer 15

*elderly
*children < 2 yo
*pregnant women
*persons with comorbidities (lung disease, heart disease, neurologic disease, renal disease, obesity)

Question 16

influenza clinical syndromes & complications: VIRAL PNEUMONIA

Answer 16

*rapid progression of fever, cough, dyspnea, hypoxia
*acute respiratory distress syndrome (ARDS) can result
*high mortality rate
*highest risk = heart disease, pregnancy

Question 17

2 organisms important for post-influenza bacterial pneumonia

Answer 17

1. strep pneumo
2. staph aureus!

Question 18

influenza clinical syndromes & complications: SECONDARY BACTERIAL PNEUMONIA

Answer 18

*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

Question 19

pathogenesis of secondary bacterial pneumonia after influenza virus

Answer 19

*destroyed/damaged physical barriers of the respiratory mucosa
*immune system dysfunction (increased glucocorticoid levels)
*increased bacterial adherence (neuraminidase-mediated)

Question 20

influenza clinical syndromes & complications: MYOSITIS & RHABDOMYOLYSIS

Answer 20

*more common in children
*muscle tenderness, especially in the legs
*markedly elevated serum creatinine phosphokinase (CPK) levels

Question 21

influenza clinical syndromes & complications: CNS involvement - Guillain Barre Syndrome

Answer 21

*ascending, progressive, symmetric muscle weakness
*absent or depressed deep tendon reflexes

Question 22

influenza clinical syndromes & complications: CNS involvement - Reye syndrome

Answer 22

*rapidly progressive encephalopathy and hepatic dysfunction in children
*aspirin use is a risk factor
*peak in 1980s, less common now

Question 23

influenza clinical syndromes & complications: MYOCARDITIS & PERICARDITIS

Answer 23

*not uncommon
*many people will present in ICU with this

Question 24

important antiviral agent used for influenza

Answer 24

OSELTAMIVIR

Question 25

oseltamivir - uses and MOA

Answer 25

*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

Question 26

influenza vaccination

Answer 26

*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

Question 27

influenza vaccine efficacy

Answer 27

*efficacy 70-90%, depending on circulating strains & host population
*reduces risk of respiratory illness, pneumonia, hospitalization, death
*cost effective

Question 28

adenovirus - overview

Answer 28

*DNA virus
*10% of respiratory infections
*outbreaks among children, young adults, military

Question 29

adenovirus - clinical manifestations, diagnosis, treatment

Answer 29

*fever, pharyngitis
*conjunctivitis
*pneumonia
*myocarditis
*hemorrhagic cystitis
*hepatitis
*diagnosis: PCR
*tx: supportive

Question 30

SARS-CoV-2 - overview

Answer 30

*enveloped, RNA virus in the coronaviridae family
*transmitted by aerosols, droplets
*adapts with genetic evolution and developing mutations
*disease: COVID-19

Question 31

SARS-CoV-2 - clinical manifestations

Answer 31

*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

Question 32

SARS-CoV-2 - antivirals

Answer 32

*remdesivir (inhibits RNA polymerase)
*nirmatrelvir with ritonavir (inhibits viral protease)

Question 33

SARS-CoV-2 - binding mechanism

Answer 33

*receptor-binding domain (RBD) of spike protein binds to ACE2

Question 34

SARS-CoV-2 - immune modulators

Answer 34

*suppress hyperinflammation due to COVID-19 (ex. corticosteroids, IL-6 inhibitors, JAK inhibitors)

Question 35

SARS-CoV-2 - monoclonal antibodies

Answer 35

*mAbs block entry of SARS-CoV-2 into human cells and neutralize the virus

Question 36

SARS-CoV-2 - mRNA vaccines

Answer 36

*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

Question 37

SARS-CoV-2 - protein subunit (adjuvant) vaccines

Answer 37

*spike protein fragments
*95-99% effective in preventing moderate to severe disease

Question 38

paramyxoviruses

Answer 38

*enveloped, RNA viruses
*RSV, parainfluenza (croup), measles, mumps

Question 39

respiratory syncytial virus (RSV)

Answer 39

*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

Question 40

measles

Answer 40

*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)