Genetics & Virology
 
 

 

Severe acute respiratory syndrome coronavirus 2

(SARS-CoV-2)

Respiratory syncytial virus (RSV)

Influenza A virus (IAV)
    • Baltimore Class IV: non‐segmented, positive‐sense single‐stranded RNA (+ssRNA) genome
    • Belonging to Betacoronavirus with club-shaped spike (S) glycoprotein trimers on the enveloped virion, binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of the airway epithelial cells
  • Genomic RNA functioning as polycistronic mRNA can be directly translated into protein inside the host cell.
      • Baltimore Class V: non‐segmented, negative‐sense single‐stranded RNA (−ssRNA) genome
      • Belonging to Pneumovirus with trimeric fusion (F) glycoproteins expressed on the enveloped virion, binding to IGFR1 and nucleolin on the surface of the ciliated airway epithelial cells
    • The negative-sense RNA genome serves as the template for mRNA transcription and genome replication, carried out by the viral RNA-dependent RNA polymerase.
    • Baltimore Class V: eight segments, negative‐sense single‐stranded RNA (−ssRNA) genome
    • Belonging to Alphainfluenzavirus with trimeric hemagglutinin (HA) glycoproteins decorated on the enveloped virion, binding to sialic acids on the surface of the airway epithelial cells
  • The negative-sense RNA genome is transcribed and replicated by the viral-RNA-dependent RNA polymerase to produce capped and polyadenylated mRNAs.

 

 

Transmission Routes & Course of the Disease
 
 

 

 

 Severe acute respiratory syndrome coronavirus 2

(SARS-CoV-2)

Respiratory syncytial virus (RSV)

Influenza A virus (IAV)
    • Direct or indirect exposure to infectious respiratory fluids: airborne droplets and aerosol particles
    • The mean incubation period is five days (2~14 days) after exposure.
    • The median duration of illness is 7~14 days after symptom onset.
  • The mean duration of shedding infectious virus is 6~20 days after initial symptom onset, even though asymptomatic or after symptom resolution, up to 63 days
    • Direct or close contact with contaminated secretions, usually large droplets.
    • Following an incubation period of 4~6 days, it can start to have symptoms.
    • The median duration of symptoms at presentation was 3~5 days, and most people recover in one to two weeks, usually keeping contagious for 3 to 8 days.
  • Persons with weakened immune systems and young children may continue to shed the virus for as long as 4 weeks. 
    • Transmission between humans: direct contact, indirect contact, respiratory droplets, or aerosols
    • Sporadic transmission between humans and animals (avian and swine): close contact with virus-laden secretions
    • The incubation period is often less than three days, and most people will recover in a few days to less than two weeks.
  • Multiple IVA strains and other zoonotic flu virus types cause recurring infections.

 

 

Clinical Manifestations
 
 

 

Severe acute respiratory syndrome coronavirus 2

(SARS-CoV-2)

Respiratory syncytial virus (RSV)

Influenza A virus (IAV)
    • Asymptomatic to mild illness: fever, cough, sore throat, malaise, headache, myalgia, etc.
    • Moderate illness: shortness of breath (SpO2 ≥95%), dyspnea, or abnormal chest imaging
  • Severe to critical illness: respiratory failure (SpO₂ <95%), lung infiltrates >50%, septic shock, and/or multiple organ dysfunction
  • The common manifestations include cough, dyspnea, sputum production, tachypnea, wheezing, and sometimes fever which may appear in stages instead of all at once.
  • Concurrent or secondary bacterial infection is uncommon, but caregivers should be aware of the risk.
  • Uncomplicated type A influenza is characterized by sudden onset of fever, myalgia, headache, malaise, nonproductive cough, sore throat, and rhinitis
  • Severe IAV infection leads to bilateral pulmonary infiltrates and hypoxemia, which defines acute respiratory distress syndrome (ARDS) and accounts for high mortality.

 

 

 

Long-Term Complications or Sequelae
 
 

 

Severe acute respiratory syndrome coronavirus 2

(SARS-CoV-2)

Respiratory syncytial virus (RSV)

Influenza A virus (IAV)

    • Fatigue and brain fog (cognitive dysfunction)

    • Dyspnea (impaired lung function)

    • Arthralgia and muscular weakness

    • Hypercoagulation and thromboembolism

    • Palpitations and chest pain (myocardial injury)
  • Associated with some respiratory morbidity: recurrent wheezing, persistent airway obstruction, decreased lung function, and bronchial hyperresponsiveness, possibly developing into allergic sensitization or asthma
  • Cardiac, pulmonary, and neurological complications are uncommon but life-threatening if left untreated or neglected

 

 

 

Diagnosis
 
 

 

Severe acute respiratory syndrome coronavirus 2

(SARS-CoV-2)

Respiratory syncytial virus (RSV)

Influenza A virus (IAV)

    • Clinical laboratory test: multiplex (a primer set) real-time quantitative reverse transcription PCR (RT-qPCR) to detect viral RNA in sample material from the upper or lower respiratory tract

    • Clinical laboratory test: serological assays (ELISA) to measure the amount of IgG, IgM, or IgA antibodies against viral antigens in human serum or plasma

    • Rapid diagnostic test (RDT) to detect viral proteins or IgM/IgG antibodies specific to these proteins

  • Rapid diagnostic test (RDT) to detect viral proteins or IgM/IgA antibodies specific to these proteins

  • Imaging tests (chest radiographs) can check for pneumonia and bronchiolitis

  • Common tests like cultures of blood and urine are performed in febrile infants for RSV-related bronchiolitis because of an association between bronchiolitis and urinary tract infections (UTIs)

  • A wide array of diagnostic tests is available, including rapid molecular assays (RT-qPCR or other nucleic acid amplification tests), rapid influenza antigen detection tests (RIDTs), and direct fluorescence assays (DFAs).

  • Platforms using the LAMP (loop-mediated isothermal amplification) technique can produce results within 20 minutes.

  • Many molecular tests can identify different types (A, B, and C) or subtypes (e.g., H1N1 or H3N2) of influenza viruses.

 

 

 

Prevention & Treatment
 
 

 

Severe acute respiratory syndrome coronavirus 2

(SARS-CoV-2)

Respiratory syncytial virus (RSV)

Influenza A virus (IAV)

    • Vaccination:

      ◇ Comirnaty® (tozinameran; mRNA type)

      ◇ Spikevax® (elasomeran; mRNA type)

      ◇ Vaxzevria®/Covishield® (ChAdOx1-S [recombinant]; viral vector type)

      ◇ Nuvaxovid® (SARS-CoV-2 rS [Recombinant, adjuvanted]; recombinant subunit type)

    • Pre-exposure prophylaxis: Evusheld® (tixagevimab plus cilgavimab)

    • Antiviral medication:

      ◇ Paxlovid® (nirmatrelvir with ritonavir) as oral tablets

      ◇ Lagevrio® (molnupiravir)

      ◇ Veklury® (remdesivir) for IV injection

  • Vaccination: currently no approved vaccine for RSV prevention, but coming two promising candidates

    ◇ RSVpreF (PF-06928316)

    ◇ RSVPreF3 (GSK3888550A)

  • Passive immunization for the broad infant population:

    ◇ RespiGam® (RSV-IGIV): an immune globulin intravenous (IGIV) human plasma product with high titers of neutralizing antibodies against RSV

    ◇ Synagis® (palivizumab)

    ◇ Beyfortus® (nirsevimab, extended serum half-life)

  • Antiviral medication:

    ◇ Virazole® (aerosolized ribavirin) for inhalation solution

  • Vaccination:

    ◇ Quadrivalent influenza vaccine is annually formulated and designed to protect against four different flu viruses, including two influenza A viruses (H1N1 and H3N2) and two influenza B viruses (Victoria and Yamagata).

    ◇ Fluzone® High-Dose Quadrivalent: inactivated type; containing a four-fold higher antigen content per dose than standard influenza vaccines to stimulate stronger immune responses

    ◇ Flublok® Quadrivalent: recombinant subunit type

  • Antiviral medication:

    ◇ Relenza® (zanamivir) for inhalation solution

    ◇ Tamiflu® and generic (oseltamivir phosphate)

    ◇ Xofluza® (baloxavir marboxil) as oral tablets

 

 

 

 

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