II. Respiratory Diseases

Mucociliary Escalator

• Composed of cilia lining the trachea and bronchi.

• Propels material, including microbes trapped in mucus, up and out of the respiratory tract.

• Swallowing, coughing, and sneezing help move microbes out.

• Infections like influenza can cause infected epithelial cells to die, compromising this defense mechanism.

Normal flora of respiratory system

• Competes with invading pathogens and helps prevent colonization.

• Resident microflora may include some potential pathogens like Streptococcus pyogenes, Staphylococcus aureus, Streptococcus pneumoniae, and Neisseria meningitidis.

COVID-19

• Abbreviation for coronavirus disease 2019.

• Caused by SARS-CoV-2.

• A single-stranded RNA virus (genes coded in RNA). Specifically, it's a positive-stranded RNA virus.

• Part of the Coronavirus family, which is large and common in people and many animal species like camels, cattle, cats, and bats. The name comes from the crown-like appearance under electron microscope.

• Virus structure includes proteins with key functions in its cycle:

  • Spike proteins (S): Mediate attachment to host cells via their ACE-2 receptors. They are heavily glycosylated and form distinct surface spikes. They utilize an N-terminal signal sequence for access to the endoplasmic reticulum and are cleaved by host cell proteases.

  • Nucleocapsid protein (N): Binds to and packages the viral RNA genome.

  • Envelope protein (E): A transmembrane protein involved in virus assembly and release; needed for pathogenesis.

  • Membrane protein (M): The most abundant protein, promotes membrane curvature and binds the nucleocapsid.

  • Hemagglutinin esterase dimer protein (HE): Found in some coronaviruses, enhances cell entry and virus spread.

• Attaches to cells via ACE-2 receptors and replicates in the respiratory tract. ACE-2 receptors are found in various locations in the body.

• The virus can multiply deep in the lungs and enter the bloodstream.

• Its recent emergence is likely from an animal reservoir, spreading via human-to-human transmission.

• Symptoms and signs vary from mild to severe, appearing 2-14 days after exposure.

• Common symptoms include fever, cough, and shortness of breath.

• Seek medical attention for trouble breathing, persistent chest pain/pressure, confusion, inability to get up, or blue lips/face.

• Can cause mild follicular conjunctivitis.

• Prevention: Disinfection (viral envelope susceptible to >70% alcohol) and masks (reduce spread of viral particles).

• Treatment: No specific medicine for prevention or treatment mentioned. Self-care like rest, fluids, warmth, humidifiers/steam for symptoms are suggested.

• Tests are primarily PCR-based (RNA detection) or serological (antibody detection).

• Vaccination challenges mentioned include the virus not reproducing well in chicken eggs (unlike flu) and the financial risks posed by the pandemic without knowing safety and efficacy.

• Long Covid is a risk not linked to the initial symptom severity. A study showed ~5-8% of patients have persistent symptoms past 4 weeks.

Influenza

• Annual epidemics are a concern, with 3,000-49,000 deaths/year in the US.

• Seasonal flu: Causes 80-90% of flu-related deaths in individuals ≥ 65 years old. Flu season in the US is typically Oct-May. The seasonal vaccine targets the strains predicted to be most common. Traditional vaccines are quadrivalent (protect against 4 viruses), usually heat killed; nasal mist is attenuated. Vaccines are commonly made in chicken eggs, but mammalian cells or recombinant methods (using HA protein) can also be used.

• 1918 Spanish flu: Killed over 50 million people globally. Predominantly affected previously healthy young adults. Killed through a cytokine storm (overreaction of the immune system). Started in birds. Spread through sneezes/coughs (up to half a million particles). Had high mortality (up to 20% overall, 70% in pregnant women). Showed a W-curve mortality pattern. Research has involved reconstructing this virus.

• H1N1 pandemic: First seen in the US in Spring 2009. Very contagious, spreading person-to-person. Spread worldwide; most cases were mild to moderate. High-risk groups for complications included pregnant women, young children, diabetics, asthma, heart disease, etc..

• Avian flu ("Bird Flu") strains (H5N1, H7N9): H7N9 was deadly to humans but not birds 10 years ago; now deadly to birds (<24hr death for chickens) and still deadly to humans (>1/3 die). H5N1 has been spreading since 2005 and has a high human mortality rate. Both H5N1 and H7N9 do not spread easily person-to-person currently, but there are fears they could make that jump. Research has manipulated H5N1 to be more transmissible in ferrets, leading to discussions about "gain-of-function" research risks and ethical implications.

• Symptoms include cough, weakness, fatigue, muscle aches.

• Transmission is via aerosol, inhaled into the lungs.

• Secondary lung infections often follow.

• Complications are serious in the very young, elderly, pregnant women, and immunocompromised.

• Influenza viruses infect birds, hogs, horses, seals, and other mammals.

• Vaccines are available and needed annually.

• The virus shows significant immunological variation. Concerns exist about the next pandemic.

• Antigenic drift: The influenza virus genome is variable, with frequent mutations in surface glycoproteins (HA and NA) recognized by the immune system. This is the reason for the need for a new flu shot every year.

• Antigenic shift: Occurs when two different flu viruses infect the same host, allowing viral genome segments to be swapped. This can result in a new virus totally unrecognized by the human immune system. Influenza A virus has 8 RNA segments coding for 11 genes.

Pneumonia

• Defined as inflammation of the lungs, where alveoli fill with fluid.

• Can infect one or both lungs.

• Caused by bacteria or viruses.

• Common Bacterial Pathogens: Streptococcus pneumoniae, Legionella pneumophila, Haemophilus influenzae, Mycoplasma pneumoniae, Klebsiella pneumoniae.

• Common Viral Pathogens: SARS, COVID-19, Hantavirus, Influenzas, Respiratory syncytial virus.

• Causes > 2 million cases and 45,000 deaths annually in the U.S..

• Early symptoms are similar to the common cold, including fever, chest pain, difficulty breathing, and discolored sputum.

Tuberculosis (TB)

• Caused by Mycobacterium tuberculosis.

• Characteristics: Acid fast, lipid-rich cell wall, resistant to disinfectants and drying. It is a rod-shaped bacterium.

• Spread is via the respiratory route.

• Has a low infectious dose.

• Infects lungs, lymph nodes, etc.. Can multiply within macrophages and migrate within them throughout the body.

• Symptoms include chronic fever, weight loss, and cough.

• Chronic/latent infections can often reactivate.

• Prevention: A vaccine is used in some countries.

• Treatment: Antibiotics are used, but resistance is a problem. Long-term antibiotic therapy (up to 12 months) is needed.

• The Tuberculin test is used for early detection.

• A related bacterium, Mycobacterium paratuberculosis, causes Johne’s disease, an intestinal disease of ruminants.

• Globally, 1/3 of the world population harbors TB bacteria (~2 billion people).

• M. tuberculosis is an important pathogen attacking patients with AIDS. HIV and TB co-infections are very problematic worldwide, especially in developing nations. 1/3 of HIV-infected people are co-infected with M. tuberculosis. TB is a cause of death for many suffering from AIDS.

Whooping Cough

• Caused by Bordetella pertussis.

• An encapsulated, gram-negative, rod-shaped bacterium.

• Attaches to host cells for survival. Produces virulence factors that damage tissue. Contains LPS with unusual structures.

• An upper respiratory infection.

• Early symptoms are similar to the common cold.

• Followed by violent cough attacks where gasping for air makes a "whooping" sound.

• Extremely serious in babies under 6 months old.

• Highly contagious.

• Treatment with antibiotics is available.

• Vaccination and boosters are needed for prevention.

Common Cold

• Over 75% of cases are caused by Rhinoviruses.

• Rhinoviruses are small (20 nm), icosahedral particles with a single-stranded RNA genome.

• Over 100 different strains or serotypes are known. Exposure to one strain does not protect against future infections by other strains.

• Rhinoviruses are members of the Picornavirus family, which includes poliovirus and foot and mouth disease virus.

• Infects mucous membranes lining the nose and throat.

• Can survive several hours on skin and up to 4 days on inanimate surfaces.

• Aerosol spread is the most common mode of transmission; sneezing is very effective at spreading the virus.

• Causes 62 million cases yearly in the U.S., resulting in 45 million missed days of school or work.

• Most infections remain symptomless.

• Symptoms (coughing, sneezing, runny nose) are primarily caused by the body’s immune response to the infection.

• Stress can increase the severity of symptoms.

• Symptoms typically last about one week.