Summary of COVID-19 disease features, the research questions these raise, and potential therapeutic relevance
| Disease features | Research question | Potential therapeutic consequences |
| Clinical/demographic | ||
| Delay between infection and pneumonia | Related 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 group | Driven 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/comorbidities | Related 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 background | Related to ACE2 expression, comorbidities and/or socioeconomic factors? | Improved identification of at-risk subjects |
| Prolonged disease course | What mechanisms maintain the lung infiltrations? | Therapies to help clear pneumonic infiltrates |
| High mortality | Detailed postmortem studies to identify causes | Improved management of severe cases |
| Investigations/radiology/physiology | ||
| Marked increase in inflammatory markers | What 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 markers | Relationship to disease subtypes and outcome? | Endotyping for targeted treatments |
| Evidence of cardiac/other extrapulmonary disease | Role for poor outcomes? | Specific targeted therapies |
| Evidence for microangiopathic and macroangiopathic thromboses | Role for disease pathogenesis/poor outcomes? | Potential role for anticoagulation |
| Radiological patterns | Relationship 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 ventilation | What 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 pneumonia | Is 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 disease | Which 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.