Severe Hypoxemia in Early COVID-19 Pneumonia

To the Editor:

Luciano Gattinoni is widely acknowledged and respected for his work on acute respiratory distress syndrome, and this time he has suggested a very interesting concept describing the pathophysiology of the atypical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–induced respiratory failure (1). Based on detailed observation of several cases, the hypothesis of dividing the time-related disease spectrum within two primary “phenotypes,” type L and type H, looks logical and might be helpful in the management of patients with coronavirus disease (COVID-19). The suggested cause of hypoxemia in type L is the loss of regulation of perfusion and loss of hypoxic vasoconstriction. Hypoxemia, leading to increased minute ventilation, primarily by increasing the Vt (up to 15–20 ml/kg), is associated with a more negative intrathoracic inspiratory pressure, and the magnitude of this pressure swing is projected as a factor that may determine the transition from the type L to the type H phenotype. However, the authors did not give an explanation for loss of regulation of perfusion and loss of hypoxic pulmonary vasoconstriction.

We believe that diffuse pulmonary microvascular thrombosis is the cause of hypoxemia in early pneumonia by SARS-CoV-2. The histologic and immunohistochemistry studies suggest that in severe COVID-19 infection, a catastrophic, complement-mediated thrombotic microvascular injury occurs, with sustained activation of the actin pathway and lectin pathway cascades (2), leading to the recommendation of the use of early anticoagulation with low-molecular-weight heparin (3).

We agree with the authors that to reverse hypoxemia, oxygenation by high-flow nasal cannula may be tried in patients with type L. However, we have reservations on the “early intubation and the use of PEEP [positive end-expiratory pressure] to prevent the transition to type H,” as the authors themselves have suggested that “the lung conditions are too good.” Effective oxygenation using high-flow nasal cannula/extracorporeal membrane oxygenation in type L should prevent pleural pressure swings and self-inflicted lung injury, leading to transition to type H. Additionally, some degree of “permissive hypoxemia” (4) may also be accepted in patients with type L to avoid ergotrauma, caused during ventilating the compliant lungs.

However, other patients, who worsen to type H because of cytokine storm, as the authors have suggested, should be treated as severe acute respiratory distress syndrome, including higher positive end-expiratory pressure, if compatible with hemodynamics, prone positioning, and extracorporeal support.