03-11-22 – COVID Flashcards
Learning outcomes
- Understand the relevance of SARS-COV2 and COVID-19 in general
- Understand the priorities in acute care of COVID
- Understand the key areas for development, with an emphasis on COVID-19 treatments
- Understand the critical role of clinical research in medicine today
What are the origins of SARS-COV2?
What is its structure like?
What corona virus number does it cause?
What are the 4 main structural proteins that make up SARS-COV2?
What do mutations in spike proteins cause?
What is a current circulating variant of concern?
- The Origins of SARS-COV2 are likely from natural virus entry from a bat, via intermediate
- Its structure is a single-stranded RNA virus
- SARS-COV2 causes Coronavirus number 7
- 4 major structural proteins that make up SARS-COV2 (NMES)
1) Nucleocapsid
2) Membrane
3) Envelope
4) Spike - Mutations in spike proteins lead to inevitable variants with different structure, function, and enhanced overall fitness
- A current circulating variant of concern is Omicron (WHO label)
What are the 2 main methods SARS-COV2 enters cells?
- 2 main methods SARS-COV2 enters cells:
1) Endocytosis
2) TMPRSS2 (Transmembrane serine protease 2)
What are 12 possible symptoms of Covid?
What are 4 of the most common symptoms?
What may be the only symptom?
- Possible symptoms of Covid:
1) Fever or chills
2) Cough
3) Malaise (a general feeling of discomfort, illness, or unease whose exact cause is difficult to identify)
4) Shortness of breath or difficulty breathing
5) Fatigue
6) Myalgia (Muscle or body aches)
7) Headache
8) New loss of taste or smell
9) Sore throat
10) Congestion or runny nose
11) Nausea or vomiting
12) Diarrhoea - 4 of the most common symptoms:
1) Fever
2) Cough
3) Malaise
4) SOB - Patients may only present with diarrhoea and vomiting, or present with no symptoms at all
What are 5 overt (obvious) signs of covid that can be seen on examination/tests?
- 5 Overt (obvious) signs of covid that can be seen on examination/tests:
1) Pneumonia or bronchial breathing
* Presence/absence of pneumonia can often indicate how well a patient will do
* Bronchial breath sounds are loud, harsh breathing sounds with a midrange pitch.
* Doctors usually associate them sounds with exhalation, as their expiratory length is longer than their inspiratory length.
* Bronchial breath sounds are normal as long as they occur over the trachea while the person is breathing out
2) Frequently signs on chest – bilateral signs (fine crepitations on exam/CXR)
* Crackles or crepitations are short, explosive sounds heard on auscultation of the chest
3) Respiratory failure
4) Acute kidney injury
5) Delirium
* Delirium is a state of mental confusion that can happen if you become medically unwell
What are 4 prognostic biomarkers of covid?
What are 3 severity markers of covid?
What pneumonic can be used for risk factors for covid?
- 4 prognostic biomarkers of covid:
1) lymphopenia (<1.0) – low white blood cells
2) Elevated Ferritin
3) Elevated LDH
4) Elevated D-dimer (>1000ng/ml) - 3 severity markers of covid:
1) SOFA
2) qSOFA
3) lactate >4 mmol/l - Pneumonic for risk factors of covid (SO AFRAID):
1) S – Sex
2) O – Obesity
3) A – Age (>60)
4) F – Frailty
5) R – respiratory disease
6) A- cArdiovascular disease
7) I – Immunosuppression
8) D - Diabetes
What is ISARIC?
What were 3 findings from ISARIC studies in the UK on covid?
- ISARIC is a global federation of clinical research networks, providing a proficient, coordinated, and agile research response to outbreak-prone infectious diseases.
- Findings from ISARIC studies in the UK on covid:
1) Covid was more common in men in the study
2) The greater the age, the greater the number of risks that come with having covid
3) Cough, fever, SOB, fatigue were the most common symptoms on presentation in the hospital
How does acute covid present?
How long is the pre-symptomatic stage?
What 3 things do we need to consider with acute covid?
How is suspected/mild covid treated different based on presence of (in picture – other comorbidities):
* Mild illness?
* Pneumonia?
* ARDS (acute respiratory distress syndrome)?
* Sepsis (severe sepsis/septic shock)?
- A majority of patients with acute covid have low or minimal symptoms of infection
- We also have to note the pre-symptomatic stage, which is about 3 days
- 3 things we need to consider with acute covid:
1) Mild illness (self-resolving) vs acute disease (subtype, severity)
2) Urgent/immediate treatment priorities
3) Ceiling of care
* Refers to the maximum level of care which the patient is set to receive,
* This is often a complex and sensitive decision reached between the patient, their family and the healthcare team responsible for the patient.
What are 5 ways to diagnose covid?
- Way of diagnosing Covid:
1) Nose/throat swab RT-PCR
2) Genomics (‘WGS’ – whole genome sequencing)
3) Measure of viral presence (not disease, as they could be ill for other reasons but so happen to have or not have the virus)
4) Antibody testing
5) Imaging, such as CXR, then comparison to ECG
What are 3 pros and 4 cons of Nose/throat swab RT-PCR?
- 3 pros of Nose/throat swab RT-PCR:
1) Positive diagnosis (tells us virus is there, no discussion)
2) Clinically relevant
3) Rapid test (lab PCR 2-3h) - POCT (20mins) (points of care testing – LFT)
- 4 cons of Nose/throat swab RT-PCR:
1) Negative does NOT = no infection
2) Operator-dependent
3) Upper airway virus (may not swab virus)
4) Test failure/performance
Why is WGS (whole genome sequencing) used for covid?
When might urgent samples be sequenced?
- WGS (whole genome sequencing) is used for covid as it allows scientists to classify a virus as a particular variant and determine its lineage.
- Urgent samples come from cases where it is unclear how they might have been infected, or when additional evidence is needed to confirm which cluster they belong to
What is antibody testing not relevant for?
Do antibodies equate to immunity?
What is the host antibody response to covid?
What else we have to consider for antibody testing?
- Antibody testing for covid is not relevant for acute COVID diagnosis, as they may have old antibodies from an old covid infection/vaccine
- Antibodies do not equate to immunity
- Host antibody immune response to covid is IgM (>10d), and later IgG (~6-12 months)
- We also need to consider what is required for the antibody test, and constantly update this
- E.g 2021: seronegative patients offered monoclonal antibody treatment (‘Ronapreve’)
- 2022: Ronapreve ineffective
Predominantly, what type of illness is covid?
How are CXRs used in covid?
What 3 things is a CXR sensitive to that can be related to covid?
Why is a normal CXR reassuring?
What % of people with covid have mild or moderate cases of covid?
What will moderate covid include on an x-ray?
What are the most commonly reported signs of covid on a CXR/CT scan?
What is bilateral interstitial pneumonia? What is ground-glass opacity (GGO)?
- COVID-19 is predominantly a respiratory illness
- CXR is a critical diagnostic/prognostic marker in COVID19, and provides the most cost-effective biomarker
- 3 things a CXR is sensitive to that can be related to covid:
1) Pneumonia
2) Heart failure
3) Early ARDS (acute respiratory distress syndrome - This makes a normal CXR reassuring (when compared with ECG) that major complications are not present
- ~80% will have mild (40%) to moderate (40%) disease, most will recover
- Moderate disease will include a mild form of pneumonia on a CXR
- Bilateral infiltrates and ground glass opacity are the most commonly reported signs on CXR and CT imaging
- Bilateral interstitial pneumonia is a serious infection that can inflame and scar your lungs
- Ground-glass opacity (GGO) is a finding seen on chest x-ray (radiograph) or computed tomography (CT) imaging of the lungs.
- It is typically defined as an area of hazy opacification (x-ray) or increased attenuation (CT) due to air displacement by fluid, airway collapse, fibrosis, or a neoplastic process
What are 2 other diagnostic tools for covid?
- 2 other diagnostic tools for covid:
1) Rapid molecular diagnostics
* Performance now robust
* Still reasons to be falsely reassured (operator, timing, detection threshold)
2) Machine learning and ‘Deep Neural Networks’ (DNN)
* Neural networks are computing systems designed to recognize patterns
* Could be used for – imaging, clinical information, and background info
What are the 2 stages of Covid?
What medicine can be useful in each stage?
What is the most important in the treatment of covid?
- 2 stages of Covid:
1) Viral infection +/- viraemia
* Viremia is a medical term for viruses present in the bloodstream
* Anti-virals predicted to be useful in stage/phase 1
2) Pro-inflammatory cascade
* Anti-inflammatory or immunomodulatory therapy predicted useful in phase 2
- Augmenting host responses > mitigating viral impact in the treatment of Covid
- This is because we want our immune system to help us, not cause immunopathology, which is a lot of what this disease is
What are 3 stages in the management of Covid?
How is suspected/mild covid treated different based on presence of (in picture – other comorbidities):
* Mild illness?
* Pneumonia?
* ARDS (acute respiratory distress syndrome)?
* Sepsis (severe sepsis/septic shock)?
- 3 stages in the management of Covid:
1) Make the diagnosis
* Positive swab, Clinical diagnosis, Disease ‘phenotype’ (usually respiratory)
2) Prioritize immediate or urgent interventions
* Acute respiratory failure?
* Acute drug treatments
3) Triage to appropriate ward setting
* ICU - HDU – COVID ward (high acuity) – COVID ward (low acuity)
* Establish ceiling of care
* Ceiling of care refers to the maximum level of care which the patient is set to receive,
* This is often a complex and sensitive decision reached between the patient, their family and the healthcare team responsible for the patient.
What 6 part pneumonic do we use in the acute management of covid?
STRAPP
How is type 1 and type 2 respiratory failure classified?
What is the first line of treatment for respiratory support?
How does it work?
What are the advantages of it?
What other techniques is it used over?
What do we do if there is increased work of breathing?
- Classification of type 1 and 2 respiratory failure:
- Partial pressure of oxygen in arterial blood (paO2) <8kPa – type 1 respiratory failure
- Above and Partial pressure of CO2 in arterial blood (paCO2) >8kPa - type 2 respiratory failures
- CPAP now 1st line form of respiratory support
- CPAP is continuous positive airway pressure, meaning air is always being blown into the lungs
- CPAP provides ability to reduce efforts of breathing, recruits small airways, improves oxygenation, and minimises trauma
- CPAP is used over HFNO, which is high flow nasal oxygen therapy
- If there increased work of breathing, tiring, progressive respiratory failure (increased FiO2 to 0.60), then we discuss with ICU
How do we class Covid at:
* 0 – 4 weeks?
* 4 – 12 weeks?
* > 12 weeks?
What 3 parts of research need to be done for long covid?
- Covid classification based on time:
1) 0-4 weeks: Acute COVID
2) 4-12 weeks: early or subacute
3) >12 weeks: Post-acute COVID syndrome or ‘Long COVID’ - 3 parts of research need to be done for long covid:
1) Work/research in progress, observational studies
2) Investment in rehabilitation, psychology, neurology
3) Compare ‘chronic fatigue syndrome
What are ongoing trials for COVID?
What are 3 ways covid diagnostics are getting better?
How is STRAPP in acute management of covid developing (in picture)?
- Ongoing trials for covid include REMAP-CAP and RECOVERY (biggest covid trial in the world)
- 3 ways covid diagnostics are getting better:
1) POCT will become easier (point of care testing)
2) Role in out-patients at risk
3) Markers in ICU
