Lecture 9.2 - COVID-19_ Primary Care Perspective

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Questions and Answers

What percentage of COVID-19 cases can the Moderna vaccine prevent?

100%

95%

82.4%

94% (correct)

What is the main host receptor involved in the pathogenesis of SARS-CoV-2?

Macrophages

ACE 2 (correct)

Epithelial cells

Dendritic cells

What is the duration of the asymptomatic phase of SARS-CoV-2 infection?

A couple of days (correct)

A week

A few hours

A month

What is the mechanism of action of the Oxford-AstraZeneca ChAdOx1 nCoV-19 vaccine?

It recognises the spike protein as foreign and forms antibodies Signup and view all the answers

What is the efficacy of the Oxford-AstraZeneca ChAdOx1 nCoV-19 vaccine after the second dose?

82.4% Signup and view all the answers

Where does the initial replication of SARS-CoV-2 occur?

Upper respiratory tract Signup and view all the answers

What is the primary receptor for SARS-CoV-2 on host cells?

Angiotensin-converting enzyme 2 Signup and view all the answers

What is the likely natural host of SARS-CoV-2?

Bats Signup and view all the answers

What is the primary function of the S protein in SARS-CoV-2?

Host cell binding and entry Signup and view all the answers

What is the typical incubation period of SARS-CoV-2?

5-6 days Signup and view all the answers

What is the primary mechanism of viral mutation in SARS-CoV-2?

Errors during viral RNA duplication Signup and view all the answers

What is the result of the S protein binding to ACE2 on host cells?

Membrane fusion and release of viral genome Signup and view all the answers

What is the significance of the S2 sub-unit of the S protein in SARS-CoV-2?

Highly preserved and a potential antiviral target Signup and view all the answers

What is the result of the viral load peaking in the first week of infection?

Symptoms develop Signup and view all the answers

What is the primary function of the antibody response in SARS-CoV-2?

Neutralizes the virus Signup and view all the answers

What is the significance of the balancing act between stability and instability in viral mutations?

Limits viral transmissibility Signup and view all the answers

What is the primary mechanism by which SARS-CoV-2 enters the type 2 alveolar epithelial cells in the lower respiratory tract?

Via the host receptor ACE-2 Signup and view all the answers

Which of the following cytokines is NOT involved in the 'cytokine storm' in the lower respiratory tract?

Tumour necrosis factor-beta (TNF-beta) Signup and view all the answers

What is the primary consequence of the 'cytokine storm' in the lower respiratory tract?

Sequestration of neutrophils and CD4 helper T cells in the lung tissue Signup and view all the answers

What is the estimated percentage of patients who can be managed effectively at home with conservative measures for viral infection?

80% Signup and view all the answers

What is the primary function of Covid-19 'red sites'?

All of the above Signup and view all the answers

What is the primary outcome of the 'cytokine storm' in the lower respiratory tract?

ARDS (Acute Respiratory Distress Syndrome) Signup and view all the answers

Which of the following is NOT a non-specific symptom of COVID-19?

Diarrhea Signup and view all the answers

What is the primary role of CXCL-10 in the immune response to COVID-19?

To act as a chemoattractant for CD4 helper T cells Signup and view all the answers

What is the primary mechanism of immune response during the upper respiratory tract involvement?

Release of interferons and CXCL-10 Signup and view all the answers

What is the primary reason for the limited immune response generated during the initial phase of COVID-19?

Low viral load Signup and view all the answers

Study Notes

COVID-19 Pathogenesis

Despite low viral load, individuals are highly infectious, and the virus can be detected via nasal swab testing.
Upper respiratory tract involvement:
- Non-specific symptoms: fever, malaise, dry persistent cough.
- Can cause transient damage to olfactory epithelial cells, leading to olfactory dysfunction (loss of smell and taste).
- Greater immune response generated during this phase, involving the release of CXCL-10 and interferons (IFN-beta and IFN-gamma) from virus-infected cells.
Lower respiratory tract involvement:
- ~1/7 of all infected patients progress to this stage and can develop severe symptoms.
- Can ultimately lead to ARDS (acute respiratory distress syndrome).
- Stipulated mechanism:
  - Virus invades and enters type 2 alveolar epithelial cells via the host receptor ACE-2.
  - Undergoes replication to produce more viral nucleocapsids.
  - Release of cytokines and inflammatory markers, including IL-1, IL-6, IL-8, IL-12, TNF-alpha, IFN-gamma, and IFN-beta, CXCL-10, MCP-1, and MIP-1 alpha.
  - "Cytokine storm" acts as a chemoattractant for neutrophils, CD4 helper T cells, and CD8 cytotoxic T cells, leading to inflammation and lung injury.

Clinical Spectrum

Approximately 80% of patients can be managed effectively at home with conservative measures for viral infection.
Remote assessment and risk stratification is a clinical dilemma.
COVID-19 "red sites" set up across the country to support resilience in primary care, provide a clinically safe and effective face-to-face assessment service, and stratify clinical risk.

Vaccines

Moderna vaccine: Can prevent 94% of COVID-19 cases, and prevented all severe cases of COVID-19.
Oxford-AstraZeneca ChAdOx1 nCoV-19 (AZD1222):
- Made from a weakened version of a common cold virus (adenovirus) that is genetically engineered to make the spike protein of the SARS-CoV-2 virus.
- Immune system recognizes the spike protein as foreign, forms antibodies, and attacks the SARS-CoV-2 virus, preventing infection.
- Safety and efficacy: Clinical trials including 23,000 people in the UK showed 82.4% effectiveness after the second vaccine.

Pathogenesis - Asymptomatic Phase

Respiratory aerosols bind to epithelial cells in the upper respiratory tract.
Main host receptor is ACE 2 (nasal epithelial ++).
Local replication and propagation.
This stage lasts a couple of days.

Coronavirus History

Human coronavirus first identified in 1965.
Later that decade, researchers found a group of similar human and animal viruses and named them after their crown-like appearance.
The spherical viral particles contain cross-sections through the RNA viral genome.

Classification of Human Coronaviruses

[No specific information provided]

Naming COVID-19

[No specific information provided]

SARS-CoV-2

Enveloped beta-coronavirus.
Has a genetic sequence very similar to SARS-CoV-1 (80%) and bat coronavirus RaTG13 (96.2%).
Viral envelope is coated by spike (S) glycoprotein, envelope (E), and membrane (M) proteins.
Host cell binding and entry are mediated by the S protein.
The S1 sub-unit of the S protein contains the receptor binding domain that binds to the peptidase domain of angiotensin-converting enzyme 2 (ACE 2).

Potential Origin of SARS-CoV-2

Bats are likely reservoir hosts for SARS-CoV-2.
Inconclusive evidence if Bat-CoV RaTG13 directly jumped to humans or transmitted to intermediate hosts.
No intermediate host sample was obtained by scientists in an initial cluster of infections.
Metagenomic sequencing suggests that pangolins might be the intermediate hosts between bats and humans.

Viral Load Dynamics and Duration of Infectivity

Following initial exposure, patients typically develop symptoms within 5-6 days (incubation period).
The viral load peaks in the first week of infection, declines thereafter gradually.
The antibody response gradually increases and is often detectable by day 14.

Viral Mutations, Variants, and Strains

Mutations are errors that occur during the process of duplicating viral RNA.
Produces variants which are similar but not exact copies of the original virus.
A new strain is when a variant displays distinct physical properties to the original virus.
Viruses mutate to adapt to their surroundings and more effectively move from host to host.
Mutations can help viruses to better evade the host's immune systems, treatments, and vaccines.

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Description

This quiz covers the pathogenesis of COVID-19, including the upper respiratory tract involvement, symptoms, and immune response. It also explores the effects of the virus on olfactory epithelial cells and the detection of the virus through nasal swab testing.