Respiratory infections and COVID-19 Flashcards
What bacteria cause respiratory tract infections?
Streptococcus pneumoniae
Mycobacterium tuberculosis
Legionella pneumophila
Mycoplasma pneumoniae
What coronaviruses cause respiratory infections?
Rhinovirus
Influenza
- RSV
- parainfluenza virus
Coronavirus
- Human coronaviruses
- SARS coronavirus 2
What fungi cause respiratory tract infections?
Aspergillus fumigatus
Pneumocystis jirovecii
Which part of the respiratory tract is exposed to pathogens normally?
Lungs constantly exposed to particulate material and microbes from upper airway
Lower airways usually devoid of conventional pathogens
What are the innate immunity features in the respiratory tract?
Cilia – mucociliary escalator removing debris and pathogens
Alveolar macrophages
- secrete antimicrobials
- engulf and kill pathogens
- recruit other immune cells
- process and present antigens to T cells
What are the acquired immunity features in the respiratory tract?
B cell/T cell responses - essential for intracellular pathogens, such as mycobacteria, viruses and fungi
IgA secreted by plasma cells interferes with adherence and viral assembly
What is inflammation?
Inflammation = body’s response to insult
Acute or chronic
What are the macro features of inflammation?
Macro = redness, swelling, heat, pain and loss of function
What are the micro features of inflammation?
Micro = vasodilation, increased vascular permeability and inflammatory cell infiltration
What are the 5 infections of the upper respiratory tract?
Rhinitis
Sinusitis
Pharyngitis
Tonsillitis
Laryngitis
What are the 6 infections of the lower respiratory tract?
Bronchitis
Bronchiolitis
Pneumonia
Pulmonary tuberculosis
Pulmonary abscesses
Empyema
What is the difference between the 5 respiratory viruses?
Rhinovirus: common cold
Influenza: ‘flu’
Coronavirus: human: common cold
zoonotic: severe respiratory illness
RSV: bronchiolitis
Parainfluenza virus: croup (
Are viral UTRIs more common as children or adults?
5-7x/year in preschool children; 2-3/year in adulthood.
Colds account for _____% of all time lost from work for sickness
40%
Which respiratory illness has >200 viral subtypes associated?
Common cold
Which viruses cause the common cold?
Rhinovirus = commonest; cause 30-50%
Human coronaviruses cause about 10 to 15 percent of common colds
How are common colds transmissed?
Hand contact: virus remains viable for up to 2 hours on skin or several hours on surfaces
Droplet transmission from sneezing / coughing / breathing
What is the incubation period and symptomatic period for common colds?
IP 2-3 days; symptoms last 3-10ds, and up to 2 weeks in 25% patients.
What causes the symptoms of a cold?
Bradykinin: intranasal administration of bradykinin causes a sore throat; it also causes nasal congestion due to vasodilation
Sneezing is mediated by stimulation of the trigeminal sensory nerves - histamine mediated
Nasal discharge (snot) changes colour with increasing numbers of neutrophils (white ->yellow->green) due to myeloperoxidase
Cough is mediated by the vagus nerve – inflammation has to extend to the larynx to trigger this; hyper-reactive response in URTI
Cytokines responsible for systemic symptoms such as fever
How can you tell the difference between a cold and an influenza-like illness (’flu’)?
What is influenza caused by?
Caused by Influenza A or B virus.
When does influenza spread most?
Occurs in outbreaks and epidemics worldwide; usually in winter season, so swaps hemispheres over the course of the year.
What are the features of uncomplicated influenza?
Incubation Period 1-4 days
Abrupt onset of fever+ cough, headache, myalgia and malaise, sore throat, nasal discharge
Acutely debilitating.
Fever 38-41; otherwise examination often unremarkable
What are the risk groups for complications in influenza?
Immunosuppression or chronic medical conditions
Pregnancy or 2 weeks postpartum
Age <2y or >65y
BMI >40
What are the possible complications of influenza?
Primary viral pneumonia
Secondary bacterial pneumonia
CNS disease
Death (estimated mortality rate among people infected with influenza in the US is about 0.13 percent)
What are the 3 problems a virus must solve?
It must know how to replicate inside a cell
It must move from one infected cell to a new cell (and a new host) in order to persist in nature
It must develop mechanisms to evade host defences
How do influenza viruses enter the cell?
The influenza virus haemagglutinin surface protein (H) binds sialic acids on cell surface glycoproteins and glycolipids in the respiratory tract. This allows the influenza virus to enter the cell.
How do influenza viruses escape?
The neuraminidase (N) on the surface of the virus allows the virus to escape by cleaving sialic acid bonds – otherwise the escaping virions all clump together.
What is the benefit of the influenza virus having a segmented genome?
The influenza virus has a segmented genome (8 parts) so can reassort if 2 different viruses infect the same cell.
Complete the diagram on the lifecycle of a virus
What is antigenic drift?
These are small changes (or mutations) in the genes of influenza viruses that can lead to changes in the surface proteins of the virus: HA (hemagglutinin) and NA (neuraminidase).
What is antigenic shift?
Antigenic shift is an abrupt, major change in an influenza A virus, resulting in new HA and/or new HA and NA proteins in influenza viruses that infect humans.
What are the options for treatment and prevention of influenza?
Active immunisation – against haemagglutinin and neuraminidase components
Tamiflu = oseltamivir = a neuraminidase inhibitor
Hand hygiene and droplet precautions
What is pneumonia?
Pneumonia = infection of the lung parenchyma
How does pneumonia work?
Alveoli full of inflammation = blocks oxygen transfer
What are the symptoms of pneumonia?
Fever, breathlessness, cough, sputum production;
Hypoxia, increased respiratory rate;
Pleuritic chest pain
Sepsis
What is the role of radiology in pneumonia?
Diagnosis of pneumonia requires infiltrates on a plain CXR with supporting clinical features.
Consolidation - alveoli and bronchioles completely filled with inflammatory debris / pus / pathogens.
Heart borders or diaphragm obscured due to loss of solid-gas interface
Air bronchograms - air in larger bronchi outlined by surrounding consolidation.
What does this chest x-ray show?
Right upper lobe consolidation
Pneumonia
What does this chest x-ray show?
Right lower lobe consolidation
Pneumonia
What are the clasifications of pneumonia?
Typical versus atypical – but not very helpful, as there is no feature in an individual patient that helps distinguish between them.
Lobar versus bronchopneumonia – also not very helpful; descriptive, but doesn’t help management
Community versus hospital-acquired = much more useful, as the pathogens involved differ in their % contribution
What are community-acquired pneumonia pathogens?
Streptococcus pneumoniae
Haemophilus influenzae
Mycoplasma pneumoniae
Legionella pneumophila
Staphylococcus aureus
Respiratory viruses probably responsible for ~1/3
plus Pneumocystis jirovecii in cell-mediated immunodeficiency
& Aspergillus fumigatus
What is the commonest organism causing pneumonia?
Streptococcus pneumoniae
What are the microscopic features of Streptococcus pneumoniae?
Gram positive cocci
What are the risk factors for pneumonia due to Streptococcus pneumoniae
Alcoholics, respiratory disease, smokers, hyposplenism, chronic heart disease
HIV – 50- to 100-fold increase in invasive pneumococcal disease in HIV+
How does Streptococcus pneumoniae cause pneumonia?
Acquired in nasopharynx
Asymptomatic carriage in 40-50%
smokers>non-smokers
What is the treatment and prevention for Streptococcus pneumoniae?
Prevention – vaccine
Treatment – penicillin
What is the Commonest cause of ambulatory ‘atypical pneumonia’?
Mycoplasma pneumoniae
What is the typical presentation of Mycoplasma pneumoniae?
Classically young patient, vague constitutional upset, several weeks
Extrapulmonary symptoms very common
Which pneumonia pathogen lacks cell walls and what is the impact of this?
Mycoplasma pneumoniae
resistant to penicillins
cannot grow on normal lab plates
What is the diagnosis and treatment for Mycoplasma pneumoniae?
Diagnosis by PCR of throat swab (VTS)
Treatment: macrolides or tetracyclines
How does Legionella pneumophila infections occur?
Can occur as sporadic infection or in outbreaks associated with a contaminated water source (consider travel and nosocomial acquisition)
Which pneumonia pathogen is uncommon?
Legionella pneumophila
What are the features of pneumonia caused by Legionella pneumophila?
Can cause severe, life threatening infection
What are the risk factors for pneumonia caused by Legionella pneumophila?
Smoking and chronic lung disease
What is the diagnosis and treatment for Legionella pneumophila?
Diagnosis
- Don’t grow on routine culture – need special conditions, and longer
- Urinary legionella antigen
Treatment: macrolides or quinolones
What is healthcare-associated pneumonia?
New onset at least >48 hours since admission.
Hospitalised patients become colonised with hospital bacteria
These may either be intrinsically more resistant to antibiotics, or have acquired resistance mechanisms.
Name the pathogens which cause hospital-acquired pneumonia
- Escherichia coli
- Klebsiella pneumoniae
- Pseudomonas aeruginosa
- Staphylococcus aureus
- Streptococcus spp
What fraction of the world’s population has latent TB?
One quarter of the world’s population has latent TB
Where were the majority of UK TB patients born?
Outside of UK
What are the social risk factors for TB?
What are the pathological features of TB?
Aerobic bacillus
Divides every 16-20 hours (slow) – lab extends culture to 56 days
Cell wall, but lacks phospholipid outer membrane
- Does not stain strongly with Gram stain (weakly positive)
- Retains stains after treatment with acids
Referred to as acid fast bacillus (AFB)
What stains are used for TB?
Special stains – Ziehl-Neelsen or auramine-rhodamine
How is TB transmitted?
- Infection is initiated by the inhalation of aerosol droplets that contain bacteria.
- The initial stages of infection are characterized by innate immune responses that involve the recruitment of inflammatory cells to the lung.
- Following bacterial dissemination to the draining lymph node, dendritic cell presentation of bacterial antigens leads to T cell priming and triggers an expansion of antigen-specific T cells, which are recruited to the lung.
- The recruitment of T cells, B cells, activated macrophages and other leukocytes leads to the establishment of granulomas, which can contain Mycobacterium tuberculosis
Complete the diagram on the timeline of a TB infection
What are the features of latent TB?
Dormant bacilli
Contained by host defences
Non-infectious
Asymptomatic
Dx by demonstrating host IR
What are the features of dormant TB?
Actively replicating bacilli
May be infectious (site-dependent)
Symptomatic (site-dependent)
Dx by isolating AFBs, growing MTB or PCR positive
What are the aims and management of TB?
Cure active disease
Reduce spread
Prevent reactivation
By… 1. prompt and adequate treatment;
- appropriate source isolation;
- by contact tracing
Complete the diagram of the SARS-CoV-2 virus
What are the microscopic features of the SARS-Cov-2 virus?
Beta coronavirus
Spike protein (S) binds ACE2 receptor on airway epithelial cells (gut, other organs)
How is SARS-CoV-2 transmitted?
Likely bat in origin, to humans ?via another species
Droplet spread (+aerosol + contact)
When was SARS-Cov-2 identified and sequenced?
Identified in Dec 2019, sequenced in Jan 2020
Complete the chain of infection for COVID
What are the symptoms of COVID?
A new, continuous dry cough;
Fever over 37.8OC;
Change or loss of sense of smell or taste
COVID-19 is an illness with a wide range of symptoms.
The frequency of nausea, vomiting, abdominal pain, headache and sore throat increased with increasing age;
but fever and runny nose became less common with increasing age. Symptoms evolve over the course of the illness.
When does hospital admission usually occur with COVID?
Hospital admission is usually on days 8-10
What is COVID-19?
The clinical syndrome associated with SARS-CoV-2 infection
The spread of disease severity -
~80% of people will experience…
~15% of people will experience…
~5% of people will experience…
~80% have asymptomatic to moderate disease and recover without needing hospital treatment.
~15% may get severe disease including pneumonia.
~ 5% become critically unwell. This may include septic shock and/or multi-organ and respiratory failure.
What is the fatality rate for COVID-19?
Overall, the infection fatality rate is estimated to be 0.9% but it varies according to age and sex. It is lower in younger people (0.5% for those 45-64 years) and higher in those over 75 years of age (11.6%).
Who is most at risk from COVID?
The single greatest risk of mortality from COVID-19 is increasing age
The risk increases exponentially with age
80% of deaths have been in those aged 70 years and over,
What are the risk factors for COVID-19?
Those with underlying medical problems (hypertension, IHD, obesity, diabetes, male gender) have an increased risk of severe disease.
There is clear evidence that certain Black, Asian and minority ethnic (BAME) groups have higher rates of infection, and higher rates of serious disease, morbidity and mortality from SARS-Cov-2 infection.
Societal factors, such as occupation, household size, deprivation, and access to healthcare can also increase susceptibility to COVID-19 and worsen outcomes following infection.
What are the indicators for admission with COVID-19?
- Oxygen sats <90%
- Respiratory rate >30
- Signs of severe respiratory distress
What are the possible treatments for COVID-19?
- High risk of thromboembolism
- Glycemic issues – hyperglycemia, DKA
- Acute kidney injury
- Cardiac toxicity
- Delirium in elderly
What is the treatment for COVID-19?
Supportive care
High flow oxygen
Dexamethasone
What are the 6 preventative measures for COVID-19?
- Personal and protective equipment
- Ventilation (environment)
- Reducing encounters
- Reducing contact / proximity
- Handwashing
- Immunisation
