After SLT, the native lung may be the target of possible complications, which may be a source of morbidity or mortality [
3,
10,
11]. If the underlying pathology is pulmonary fibrosis, the native lung is exposed to infection, including mycobacterial and fungal infection, pneumothorax, hemoptysis, neoplasia in the form of bronchopulmonary cancer, or lymphoproliferative disease. In general, lung fibrosis affecting the remaining lung is not by itself directly responsible for significant morbidity. The usual profile is that of a progressive worsening of lung fibrosis over time. In 21 patients who underwent SLT for IPF and were followed for an average of 35 months after transplant, sequential high-resolution chest CT revealed a progressive loss of lung volume and extension of the fibrotic lesions over time in the native lung [
12]. Similarly, in smaller studies retrospectively analyzing 5–13 SLT patients by use of a chest CT scoring system, other investigators described progressive worsening of fibrosis (and decrease in lung volume) in the native lung [
5,
6,
8]. In contrast with the usual profile of progressive worsening of lung fibrosis, acute worsening of pulmonary fibrosis in the native lung seems to be much less frequent. The Vancouver group reported a single observation: 4 years after SLT for IPF, the patient presented acute respiratory symptoms, the chest CT revealing ground glass opacities throughout the native lung, which were not present 3 months earlier, without recent abnormalities in the grafted lung [
13]. The diagnostic workup was negative, including microbiology analysis. Within 10 days, the native lung showed progressive opacification, which led to considering the diagnosis of acute exacerbation of IPF and to administer prednisone 1 mg/kg along with
N-acetylcysteine, with subsequent improvement of the native lung on high-resolution chest CT. Despite the absence of pathology confirmation, this observation is consistent with the diagnosis of acute exacerbation of IPF on the remaining lung. Recently, Marron
et al. described three IPF patients who experienced acute worsening of pulmonary fibrosis in the native lung after SLT [
14]. All three patients were seronegative for CMV and received a graft from a seropositive donor. More than 12 months after SLT, in a context of CMV primo-infection with positive results of CMV DNA quantitative PCR in the serum, the patients presented acute hypoxemic respiratory failure. There were no radiographic or chest CT signs of CMV pneumonia affecting the graft, but within several days, opacification of the native lung was observed. The patients received CMV curative therapy, and eventually hypoxemic respiratory failure resolved, but with rapid progression of fibrosis of the native lung.
A second point common to both reports is that patients presented hypoxemic respiratory failure, along with the opacification of the native lung. In our case of CMV primo-infection, as in the three previously published cases, CMV DNA replication was detected in serum, but signs suggesting CMV pneumonia, known to mainly involve the lung allograft in case of SLT [
4], were missing on chest radiographs or chest CT. This observation raises the question of the mechanism of the hypoxemic respiratory failure presented by the patients. The severity of the parenchymal involvement of the native lung may have led to major ventilation/perfusion mismatch, with the progressive improvement of the respiratory condition mainly related to the subsequent decrease of the perfusion toward the native lung over time, rather than to antiviral treatment. Finally, both reports have in common a rapid progression of pulmonary fibrosis in a context of severe viral infection, which in our report was CMV primo-infection in one patient and COVID-19 in the other. The mechanism leading to the rapid progression of fibrosis may not be specific to CMV, but rather due to the direct viral aggression of an already injured parenchyma.