Table 1

Summary of COVID-19 disease features, the research questions these raise, and potential therapeutic relevance

Disease featuresResearch questionPotential therapeutic consequences
 Delay between infection and pneumoniaRelated to later viral replication in the lung?
Abnormal inflammation in a subset of infected subjects?
Related to development of adaptive immunity?
Antiviral treatment to prevent severe disease
Immunomodulation to prevent severe disease
 Variable severity within an age groupDriven by viral load?
Driven by genetics/epigenetics?
Driven by environmental factors?
Improved identification of at-risk subjects
Targeted antiviral/immunodulation treatments to prevent severe disease in at-risk subjects
 Increased severity with age/male sex/comorbiditiesRelated to comorbidities alone?
Direct effects on the inflammatory response?
Related to ‘inflammaging’/immunosenescence?
Improved identification of at-risk subjects
Targeted antiviral/immunodulation treatments to prevent severe disease in at-risk subjects
 High burden of disease in BAME backgroundRelated to ACE2 expression, comorbidities and/or socioeconomic factors?Improved identification of at-risk subjects
 Prolonged disease courseWhat mechanisms maintain the lung infiltrations?Therapies to help clear pneumonic infiltrates
 High mortalityDetailed postmortem studies to identify causesImproved management of severe cases
 Marked increase in inflammatory markersWhat are the mechanisms driving inflammation?
What cells are the source of inflammatory responses?
Does inflammation cause poor outcomes?
Clinical risk scoring
Improved anti-inflammatory treatment
 Variations between patients in inflammatory markersRelationship to disease subtypes and outcome?Endotyping for targeted treatments
 Evidence of cardiac/other extrapulmonary diseaseRole for poor outcomes?Specific targeted therapies
 Evidence for microangiopathic and macroangiopathic thrombosesRole for disease pathogenesis/poor outcomes?Potential role for anticoagulation
 Radiological patternsRelationship to clinical severity?
Relationship between the CT patterns over time?
Relationship between CT patterns and pathogenesis?
Clinical risk scoring
Endotyping for targeted treatments
 Severe hypoxia with low compliance ventilationWhat are the pathophysiological mechanisms?
What is the role of CPAP?
What is the best ventilation strategy?
Improved ventilatory support strategies
Pharmacological enhancement of oxygenation
Specific issues for respiratory physicians
 Survivors of severe COVID-19 pneumoniaIs there a long-term reduction in lung function? If so, who is at risk and is this related to management?
Are there other physical/psychological consequences?
Screening for impaired lung function
Acute management to reduce lung function loss
Appropriate postdischarge support
 Patients with chronic lung diseaseWhich patients with chronic lung disease are susceptible?
What mechanisms cause the increased susceptibility?
Can antivirals prevent severe COVID-19?
What proportion of patients are immune?
Improved identification of at-risk subjects
Early use of preventative therapies
Early use of antivirals
Targeted vaccination in high-risk subjects
  • BAME, black, Asian and minority ethnic; CPAP, continuous positive airways pressure.