Covid-19 pneumonia is not a straightforward disease. Chest computed tomography (CT) scans can show different versions. There is no single pattern or cluster of clinical presentations.
“Although the pulmonary pattern of critically ill patients with Covid-19 has been defined as acute respiratory distress syndrome (ARDS), it does not always represent or even resemble ARDS,” said Chiara Robba, a professor of neurology, and her colleagues at the University of Genoa.
ARDS is driven by widespread inflammation in the lungs. Fluid accumulates inside air sacs, which hampers gas exchange. Less oxygen enters the blood, depriving organs of oxygen. Its mortality rate hovers at around 40%.
The L and H Phenotypes
In April editorial in Intensive Care Medicine, Professor Luciano Gattinoni — who has been studying ARDS for decades — and his colleagues at the Medical University of Göttingen were the first to suggest that Covid-19 pneumonia has two distinct phenotypes.
- L phenotype: Low elastance (almost normal gas levels in the lungs), low ventilation to perfusion ratio (leading to hypoxemia), low lung weight, and low lung recruitability (low amount of non-aerated tissues).
- H phenotype (similar to severe ARDS): High elastance (low gas levels in the lungs), high right-to-left shunt (heart abnormality), high lung weight, and high lung recruitability (high amount of non-aerated tissues).
L phenotype is the less severe one and may either improve or transition to H phenotype. H phenotype is similar to severe ARDS and occurs about 20–30% of the time, based on their clinical case series, Professor Gattinoni noted. As follows, H phenotype (and not L) should be treated according to the standard protocol for ARDS.
The Revised 3 Phenotypes
Later in May, Professor Robba et al. added another phenotype, and now three phenotypes of Covid-19 pneumonia exist. His paper, “Distinct phenotypes require distinct respiratory management strategies in severe COVID-19,” is published in Respiratory Physiology & Neurobiology.
In the image, CT phenotypes 1 and 3 are compatible with the L and H phenotypes proposed by Professor Gattinoni, respectively. The new CT phenotype 2 is the transition phase between the other two.
Because each phenotype has different pathophysiology (patho = disease), treatment strategies need to be catered to each phenotype, they emphasized.
- PEEP ventilation is the primary treatment for each phenotype, though ventilator settings vary for each.
- CT Phenotype 1: Patients have hypoxemia (i.e., a condition of deficient levels of oxygen in the blood). Inhaled nitric oxide (i.e., a pulmonary vasodilator technique) might help. Prone positioning and recruitment manoeuvres (i.e., a technique to open collapsed areas of the lungs and keep them open) are often ineffective.
- CT Phenotype 2: Patients have atelectasis (i.e., a condition of a blocked airway that compromises gas exchange and breathing) and lung derecruitment (i.e., a condition wherein areas of the lung collapsed and lung tissues became poorly aerated). Recruitment manoeuvres might help, whereas inhaled nitrogen oxide therapy is less effective. Prone positing is most effective for this phenotype.
- CT Phenotype 3: Patients have moderate-to-severe ARDs. Prone positioning, recruitment manoeuvres, or ECMO ventilation are last-resort treatments if PEEP ventilation failed.
Extra: Phenotype vs Endotype
Endotype refers to the subtypes of a disease. Covid-19 may have pneumonia, endothelial, or neurological endotypes, for example. Within the pneumonia endotype, there can be many characteristics or traits called phenotypes, such as the L and H.
Similarly, within the neurological endotype called Neuro-COVID, there are three different phenotypes: Cerebral thrombosis with hemorrhagic infarction, demyelinating lesions, and encephalopathy.
Employing different treatment strategies for individual phenotypes of Covid-19 pneumonia is key to recovery, as the professors emphasized. Incompatible treatments might end up worsening disease prognosis.
Take proning, for instance. “We do not recommend prone positioning of Covid-19 patients with phenotype 1,” Professor Robba cautioned. “It should be reserved for phenotypes 2 and 3, to redistribute pulmonary blood flow and reduce atelectasis.”
Further, in L phenotype (or phenotype 1), “patients should be left “quiet”; avoiding doing too much is of a higher benefit than intervening at any cost,” Professor Gattinoni advised. “Understanding the correct pathophysiology is crucial to establishing the basis for appropriate treatment,” he wrote.