COVID-19

Introduction

Coronavirus disease 2019 (COVID-19) is a contagious respiratory disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

In the year since the first case of COVID-19 was reported, there were over 82 million COVID-19 cases and over 1.8 million deaths worldwide.

Aetiology

SARS-CoV-2 is primarily transmitted through respiratory air droplets, which are expelled when an infected person talks, coughs and sneezes.

SARS-CoV-2 can also be transmitted through saliva and by touching contaminated surfaces, although it significantly decays on surfaces within 72 hours.

The virus has been detected in other bodily fluids, but not at adequate viral loads to be considered infectious.

The mean incubation time (time from exposure to symptom onset) is five days, but it can be as long as 14 days.

Infectivity begins one to three days before symptom onset and can last for 10 days in mild-moderate cases, and even longer in severe cases. There are several variants of SARS-CoV-2, and more variants continue to be discovered. Some variants are more infectious than others.

Pathophysiology

SARS-CoV-2 enters nasal epithelial cells via the ACE-2 receptor and then migrates to the upper respiratory tract. This triggers an immune response, including the release of interferons (IFN-β and IFN-γ) from infected cells.

In most patients, the immune response halts the spread of the virus at the upper respiratory tract, and so most patients only develop mild symptoms. However, in approximately 20% of patients, the virus progresses to the lower respiratory tract.

Infected pneumocytes release inflammatory cytokines (such as IL-6 and IL-8), which attract immune cells to the lungs (including T helper cells).

The exaggerated immune response to SARS-CoV-2 results in diffuse alveolar damage and pulmonary oedema (in keeping with acute respiratory distress syndrome).

SARS-CoV-2 also causes damage to endothelial cells, which are found in the inner layer of blood vessels. Endothelial dysfunction results in a procoagulant state, leading to thrombotic complications (such as pulmonary embolism and microvascular thrombi in the lungs).

There is emerging evidence that SARS-CoV-2 can affect other organs (such as the brain and gastrointestinal tract), potentially through its ability to disrupt endothelial surfaces and incite exaggerated immune responses. This can cause symptoms which persist months after the acute infection (often referred to as “Long COVID”).

Risk Factors

There is an increased risk of contracting COVID-19 associated with the following:

• Close contact with an infected person (within one metre for at least 15 minutes)
• Old age
• Residence or employment in an area with increased transmission (such as healthcare settings or care homes)

The risk of developing severe COVID-19 infection is increased with:

• Male sex
• Asian and Afro-Caribbean ethnicity
• Medical comorbidities (including chronic respiratory disease, type 2 diabetes and heart failure)
• Current or former smokers

Clinical Features

History

Typical symptoms of COVID-19 include:

• Fever
• New and continuous dry cough, or one that is productive
• Altered sense of smell and taste
• Dyspnoea (initially on exertion, but may progress to resting dyspnoea)
• Non-specific symptoms such as fatigue, myalgia and pharyngitis
• Delirium and reduced mobility in the elderly

Other important areas to cover in the history include:

• Recent contact with suspected or confirmed COVID-19 cases
• Smoking history (quantified in pack-years)
• Travel history (the patient may have travelled from an endemic area)

Clinical Examination

A full respiratory examination should be performed in suspected cases of COVID-19.

Typical clinical findings in COVID-19 include:

• Tachypnoea and tachycardia
• Crepitations and bronchial breathing on auscultation
• Cutaneous manifestations such as maculopapular rash, urticaria and petechial rash

Differential diagnoses

Differential diagnoses to consider in the context of suspected COVID-19 include:

• Community-acquired bacterial pneumonia
• Influenza infection
• Common cold
• Middle East Respiratory Syndrome (MERS)
• Aspiration pneumonia

Investigations

Bedside investigations

Relevant bedside investigations include:

• COVID-19 nasopharyngeal and/or oropharyngeal swab: the swab is used to sample the respiratory mucosa. The sample is analysed using real-time reverse-transcription polymerase chain reaction (RT-PCR). A positive result indicates the presence of SARS-CoV-2 viral RNA.
• Pulse oximetry: aim for 94-98% initially, but the target saturations may be reduced to 88-92% if the patient has COPD (this is a risk-benefit judgement made by a senior clinician).
• Sputum culture: to exclude other causes of lower respiratory tract infection, including bacterial causes.
• Arterial blood gas: recommended in patients with low oxygen saturations or signs of respiratory distress. May show type 1 or type 2 respiratory failure. May also show elevated lactate, which indicates tissue hypoxia and organ dysfunction.

Laboratory investigations

Relevant laboratory investigations include:

• Full blood count: may show leucocytosis and lymphopenia
• CRP: may be elevated
• U&Es: may be elevated and indicate acute kidney injury
• LFTs: may be elevated (associated with severe disease)
• Coagulation screen: may show elevated D-dimer and prolonged prothrombin time (both associated with severe disease).

Imaging

Chest X-ray

A chest X-ray may reveal bilateral ground-glass opacifications and consolidation.

Ground-glass opacifications refer to areas of hazy opacification which do not completely obscure the underlying pulmonary vasculature or bronchial structures.

CT chest

National guidelines recommend CT chest for patients with severe disease when chest X-ray is unclear or normal (though local guidelines may vary).

Common CT chest findings include bilateral ground-glass changes, fine reticulations (linear opacifications) and peribronchovascular thickening (thickening of the connective tissue that encloses the bronchi and pulmonary arteries).

Management

Conservative management

Conservative management of COVID-19 includes:

 
• Self-isolation: all COVID-19 cases and their close contacts must self-isolate for 10 days. Self-isolation should continue after 10 days if the patient still has a fever, rhinorrhoea, malaise or diarrhoea.
 
• Symptom management: such as honey to reduce cough frequency, and discouraging patients from lying on their back as this reduces cough efficiency.
 
• Adequate hydration and nutrition.

Medical management

Medical management of COVID-19 includes:

 
• Oxygen therapy: to maintain target saturations 94-98% (or 88-92% if the patient has COPD)
 
• Antipyretics: such as paracetamol
 
• Dexamethasone: used in severe disease (such as oxygen saturations <90% on room air, sepsis or ARDS). The dose is 6mg once daily for 7-10 days.
 
• Remdesivir: this antiviral may be used in severe disease (this is a senior-led decision). Remdesivir is usually given as a loading dose of 200mg IV on day 1, followed by 100mg IV for 5-10 days.
 
• Empirical antibiotics: only recommended if bacterial co-infection is suspected. Signs of bacterial co-infection include a change in symptoms (such as new pyrexia), new neutrophilia and radiological findings suggestive of bacterial pneumonia.
 
• Venous thromboembolism prophylaxis: used in hospitalised patients as COVID-19 increases the risk of venous thromboembolism. Low-molecular-weight heparins are commonly used (such as enoxaparin).

Ventilation

Options for ventilatory support in COVID-19 include:

 
• Continuous positive airway pressure (CPAP): may be used in type 1 respiratory failure (PaO2 < 8kPa/ 60mmHg).
 
• Non-invasive ventilation (NIV): may be used in type 2 respiratory failure (PaO2 < 8kPa/ 60mmHg and PaCO2 > 6.0kPa/ 45mmHg).
 
• Mechanical ventilation: may be needed if the patient continues to deteriorate despite optimal use of CPAP or NIV.
 
• Extracorporeal membrane oxygenation (ECMO): may be needed if the patient continues to deteriorate despite mechanical ventilation and if the patient has potentially reversible respiratory failure. ECMO involves diverting the patient’s blood to an artificial oxygenator, where oxygen is added and carbon dioxide is removed from the blood. The blood is then pumped back into the patient’s circulatory system.

COVID-19: What is it and how to manage it?

Coronavirus disease 2019 (COVID-19) is a contagious respiratory disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is primarily transmitted through respiratory air droplets. Individuals are at a higher risk of contracting the disease when in close contact with an infected person. Common symptoms include continuous cough, fever and an altered sense of smell or taste.

Diagnosis of COVID-19 is based on clinical findings, detection of SARS-CoV-2 viral RNA using RT-PCR and radiological findings. Chest X-ray findings may reveal bilateral ground-glass opacifications and consolidation.

Management of COVID-19 is largely supportive in mild cases. This may involve self-isolation. In more severe cases, additional treatments such as dexamethasone and ventilatory support may be necessary.

Complications

Complications of COVID-19 include those related to the disease itself, as well as treatment-related complications.

Disease-related complications include: venous thromboembolism (e.g. pulmonary embolism), acute kidney injury, septic shock, cardiovascular complications (e.g. acute coronary syndrome and myocarditis), and “Long COVID.” This is a condition with symptoms that last 12 weeks or more, such as persistent cough, lethargy, and myalgia.

Treatment-related complications include: hyperglycaemia and confusion with dexamethasone, and ventilator-associated lung injury (VALI), ventilator-associated pneumonia (VAP) and laryngeal injury with mechanical ventilation.

Key Points

• Coronavirus disease 2019 (COVID-19) is a contagious respiratory disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• COVID-19 is primarily transmitted through respiratory air droplets. Close contact with an infected person increases the risk of developing COVID-19.
• The most common symptoms are continuous cough, fever and an altered sense of smell or taste.
• A diagnosis of COVID-19 is based on clinical findings, detection of SARS-CoV-2 viral RNA using RT-PCR and radiological findings.
• Characteristic chest X-ray findings include bilateral ground-glass opacifications and consolidation.
• Management includes self-isolation and supportive measures in mild cases. Dexamethasone and ventilatory support may be needed in severe cases.
• Complications include venous thromboembolism, septic shock and “Long COVID.”

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References

1. Gorbalenya AE et al. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology. Published in 2020. Available from: [LINK]
2. Center for Systems Science and Engineering, Johns Hopkins University. COVID-19 Dashboard. Published in 2020. Available from: [LINK]
3. Wiersinga J et al.Pathophysiology, Transmission, Diagnosis and Treatment of Coronavirus Disease 2019 (COVID-19)
4. van Doremalen N et al. published a study in the New England Journal of Medicine, with the title Aerosol and Surface Stability of SARS-CoV-2 as Compared to SARS-CoV-1. Their findings discuss how the virus is able to remain airborne and on surfaces.
5. BMJ Best Practice published a paper titled Coronavirus Disease 2019 (COVID-19). In this paper, COVID-19's pathophysiology, transmission, diagnosis, and treatment are covered.
6. McAloon C et al. conducted a rapid systematic review and meta-analysis of observational research to understand the incubation period of COVID-19. Their paper was published in 2020.
7. The World Health Organization released a paper titled Transmission of SARS-CoV-2: Implications for Infection Prevention Precautions. This document covers the implications of SARS-CoV-2 transmission.
8. Public Health England also published a document called Investigation of Novel SARS-CoV-2 Variant. It provides information on the new variant of the virus.
9. Parasher A. discussed the current understanding of COVID-19, its pathophysiology, clinical presentation, and treatment in a paper titled COVID-19: Current Understanding of its Pathophysiology, Clinical Presentation and Treatment. This paper was published in the Postgraduate Medical Journal.
10. Kumar R et al. wrote a paper titled Pathophysiology and Potential Future Therapeutic Targets Using Preclinical Models of COVID-19. This paper was published in ERJ Open Research and provides information on preclinical models of COVID-19.
11. Blanco-Melo D et al. discussed the imbalanced host response to SARS-CoV-2 and how it drives the development of COVID-19 in a paper titled Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19. This paper was published in Cell.
12. Polak SB et al. wrote a systematic review of pathological findings in COVID-19, with a pathophysiological timeline and possible mechanisms of disease progression. This paper was titled A Systematic Review of Pathological Findings in COVID-19: A Pathophysiological Timeline and Possible Mechanisms of Disease Progression and was published in Modern Pathology.
13. Jin Y et al. discussed endothelial activation and dysfunction in COVID-19, as well as potential therapeutic approaches, in a paper titled Endothelial Activation and Dysfunction in COVID-19: From Basic Mechanisms to Potential Therapeutic Approaches. This paper was published in Signal Transduction and Targeted Therapy.
14. Dennis A et al. published a paper on multi-organ impairment in low risk individuals with long COVID. It is titled Multi-Organ Impairment in Low Risk Individuals with Long Covid and was published in MedRxiv.
15. Ma C et al. wrote a paper on the effects of COVID-19 on the digestive system. This paper is titled COVID-19 and the Digestive System and was published in The American Journal of Gastroenterology.
16. Sze S et al. conducted a systematic review and meta-analysis on the differences between clinical outcomes in COVID-19 based on ethnicity. This paper is called Ethnicity and Clinical Outcomes in COVID-19: A Systematic Review and Meta-Analysis and was published in 2020.