Viral Diseases of the Respiratory System: Influenza and SARS-CoV2

Viral Diseases of the Respiratory System

Influenza Virus

The influenza virus is a major cause of acute respiratory illness worldwide. It is highly infectious and can lead to seasonal epidemics and occasional pandemics. Understanding its structure, transmission, and variation is essential for effective prevention and treatment.

• Etiology:

  • Influenza virus is a single-stranded RNA (ssRNA) virus with 8 RNA segments.

  • Capsid shape is variable.

  • Virus is enveloped.

• Virulence Factors:

  • Hemagglutinin (H): Enables virus to attach to host cell. 18 variants exist in nature. H1, H2, and H3 are most commonly associated with human infection.

  • Neuraminidase (N): Essential for virus replication and release. 11 variants exist in nature. N1 and N2 are most commonly associated with human infection.

Clinical Features and Symptoms

• Acute illness with sudden onset.

• Highly infectious; spreads rapidly person-to-person.

• Symptoms: fever, headache, muscle aches, severe weakness, cough, sore throat, difficulty breathing.

• Influenza causes stronger symptoms than the common cold (caused by coronavirus or rhinovirus).

Incubation Period

• Ranges from 1 to 4 days; most commonly 2-3 days.

• Contagiousness may persist beyond symptom onset.

Transmission

• Spread via respiratory droplets (coughing, sneezing, talking).

• Contact with contaminated surfaces followed by touching face.

Groups at Increased Risk

• Infants/toddlers (6-59 months), adults ≥50 years.

• Chronic pulmonary, cardiovascular, renal, hepatic, neurologic, hematologic, or metabolic disorders.

• Immunosuppressed individuals.

• Pregnant women.

• Children/adolescents on aspirin/salicylate medications (risk for Reye syndrome).

• Residents of nursing homes/long-term care.

Types of Influenza Viruses

• Type A: Infects humans, birds, pigs, horses; source of epidemics and pandemics.

• Type B and C: Infect humans only.

Influenza Type	Hosts
Type A	Humans, birds, pigs, horses
Type B	Humans only
Type C	Humans only

Antigenic Variation

Influenza A viruses frequently change their surface antigens, leading to new strains and challenges for immunity and vaccine development.

• Antigenic Drift: Minor changes due to natural mutations; results in new variants each year.

• Antigenic Shift: Major changes due to reassortment of RNA segments between viruses; can lead to pandemics.

Mechanisms of Antigenic Shift

• Sudden 'adaptive' change during replication of a normal virus.

• Exchange of genes between human and animal strains when co-infection occurs.

Epidemiology

• Major antigenic changes result in little/no immunity in the population.

• Allows rapid and widespread transmission.

• Examples: Drift (2003, H3N2), Shift (1957, H2N2).

Flu Pandemics

• Global epidemics of newly emerged influenza A subtypes.

• Three pandemics in the last century; worst killed 20-40 million worldwide.

• 2009 H1N1 (swine flu) pandemic.

Prevention

• Vaccines:

  • Trivalent: Protects against three strains (H1N1, H3N2, B).

  • Quadrivalent: Protects against four strains (H1N1, H3N2, B, additional B).

  • Types: Inactivated (IIV), Recombinant (RIV), Attenuated (LAIV).

  • Guidelines: All persons ≥6 months without contraindications.

Diagnosis

• Rapid tests, lab assays, and further analysis of respiratory samples.

Treatment

• Antivirals (e.g., oseltamivir, zanamivir, peramivir).

• Chemoprophylaxis within 48 hours of exposure.

• Neuraminidase inhibitors block release of new virus.

• Endonuclease inhibitor (baloxavir) interferes with viral RNA transcription.

Antiviral Agent	Activity Against	Use	Recommended For	Not Recommended For Use In	Adverse Events
Oseltamivir	Influenza A and B	Chemoprophylaxis, Treatment	3 months and older	NA	Nausea, vomiting, neuropsychiatric events
Zanamivir	Influenza A and B	Chemoprophylaxis, Treatment	7 years and older	People with underlying respiratory disease (asthma, COPD)	Bronchospasm, cough
Peramivir	Influenza A and B	Treatment	2 years and older	NA	Diarrhea
Baloxavir	Influenza A and B	Treatment	12 years and older	Pregnant women, breastfeeding mothers	Diarrhea

SARS-CoV2 (COVID-19)

Etiology

SARS-CoV2 is the causative agent of COVID-19, a severe respiratory disease that emerged in 2019. It is a single-stranded RNA virus with a nucleocapsid and an envelope, utilizing spike proteins to attach to human cells.

• Single-stranded RNA (+) virus

• Nucleocapsid and enveloped

• Spike protein binds to ACE2 receptor on human cells

• Likely originated in bats; other animals considered (e.g., pangolins)

Structure and Spike Protein

• Spike protein is a glycoprotein essential for cell entry.

• Phospholipid bilayer envelope surrounds the capsid.

• Spike protein interacts with ACE2 receptor, facilitating viral entry.

Clinical Features

• Wide range of symptoms: fever, chills, cough, shortness of breath, fatigue, muscle aches, headache, loss of taste/smell, sore throat, congestion, nausea, diarrhea.

• Symptoms may appear 1-14 days after exposure.

Diagnosis

• Antigen tests (lab or home)

• Nucleic acid amplification tests (e.g., PCR)

Epidemiology and Transmission

• Transmitted via aerosols (airborne particles)

• Prevention: vaccination, distancing, mask use, rapid detection and isolation

Treatment

• Antiviral medications: ritonavir-boosted nirmatrelvir, remdesivir, molnupiravir, interferons, ivermectin

• Antiviral treatment reduces risk of hospitalization and death in high-risk outpatients

Antigenic Variation

• Mutations in spike protein can lead to new variants with altered transmissibility and immune escape

• Persistent infections may contribute to emergence of dangerous new variants

Latent and Persistent Viral Infections

Definitions and Examples

• Latent infection: Virus remains in host cells for long periods without causing symptoms (e.g., cold sores, shingles).

• Persistent infection: Disease process occurs over a long period, often fatal (e.g., subacute sclerosing panencephalitis, prion diseases).

Graphical Representation

• Acute infection: rapid onset and resolution

• Latent infection: periods of dormancy with possible reactivation

• Persistent infection: slow progression over months or years