Different Phenotypes in COVID-19 Pneumonia Proposed

lung with infected with coronavirus
Patients with COVID-19 pneumonia may present with 2 distinct phenotypes, each warranting distinct treatments.

Based on the interaction of factors present in patients with coronavirus disease 2019 (COVID-19), authors of an editorial published in Intensive Care Medicine have developed a time-related disease spectrum within 2 phenotypes.

Although the Surviving Sepsis Campaign panel recommended that patients with COVID-19 who receive mechanical ventilation should be managed similarly to other patients with acute respiratory failure in the intensive care unit (ICU), the authors of this editorial proposed that COVID-19 pneumonia is “a specific disease, whose distinctive features are severe hypoxemia often associated with near respiratory system compliance … This remarkable combination is almost never seen in severe ARDS [acute respiratory distress syndrome].”

Therefore, based on the detailed observation of several cases and discussions with colleagues, the editorial authors hypothesized that different COVID-19 patterns found in the emergency department may depend on the interaction of the following factors: the severity of the infection, the host response, physiologic reserve and comorbidities; the ventilatory responsiveness of the patient to hypoxemia; and the time elapsed between disease onset and hospital observation.

The first phenotype, type L, is characterized by low elastance, low ventilation-to-perfusion ratio, low lung weight, and low lung recruitability. Meanwhile, the second phenotype, type H, is characterized by high elastance, high right-to-left shunt, high lung weight, and high lung recruitability. The Type H phenotype, which constituted 20% to 30% of patients in the editorial authors’ case series, fit the severe ARDS criteria, including hypoxemia, bilateral infiltrates, decreased respiratory system compliance, increased lung weight, and potential for recruitment.

The editorial authors proposed the following sequence of events to conceptualize these phenotypes: “the viral infection leads to subpleural interstitial edema (ground glass lesions) particularly located at the interfaces between lung structures with different elastic properties where stress and strain are concentrated.” They also noted that patients with Type L phenotype may remain unchanged for a period of time and then improve or worsen. The depth of the negative intrathoracic pressure associated with the increased tidal volume in spontaneous breathing may be a key feature in determining the evolution of disease. “Indeed, the combination of a negative inspiratory intrathoracic pressure and increased lung permeability due to inflammation results in interstitial lung edema,” the editorial authors noted.

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The transition from Type L to Type H may be the result of COVID-19 pneumonia or due to lung injury attributable to high-stress ventilation. The management of respiratory therapy should be tailored to each phenotype. The first step should be to reverse hypoxemia through an increase in fraction of inspired oxygen to which the patient with Type L responds well to, especially if they have not already become breathless. High-flow nasal cannula, continuous positive airway pressure, or noninvasive ventilation may be used in patients with Type L with dyspnea. The transition from Type L to Type H may be affected by the magnitude of inspiratory pleural pressure swings. For example, the risk for lung injury increases when esophageal pressure increases beyond 15 cmH20. The editorial authors also outlined potential treatment protocols for Type L patients once they are intubated as well as Type H patients being managed as having severe ARDS.

The editorial authors concluded that patients with Type L or Type H are best identified by computed tomography scan, but if not available, respiratory system elastance and recruitability can be used as surrogates.


Gattinoni L, Chlumello D, Calroni P, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? [published online April 14, 2020]. Editorial. Intensive Care Med. doi:10.1007/s00134-020-06033-2