Reply to the Letter to the Editor: “Association of subpleural ground-glass opacities with respiratory failure and RNAemia in COVID-19”

by Nagaoka K, Kawasuji H, Wakasugi M, Noguchi K, Morinaga Y, and Yamamoto Y (knagaoka@med.u-toyama.ac.jp)

Association of subpleural ground-glass opacities with respiratory failure and RNAemia in COVID-19

Dear Editor,

We thank Furkan Ufuk for his letter and interest in our study [1].

First, this study focused on the radiological patterns in the early phase of SARS-CoV-2 infection between April 2020 and October 2021 (when the vaccine had not been available in Japan). Therefore, the patient’s inclusion was limited to those with unenhanced chest CT performed upon admission (within 7 days after symptom onset). The median CT-evaluated day of whole cohort was 3 [interquartile range: 2-5] days after symptom onset. The nasal-swab viral load and RNAemia were evaluated on the CT-evaluated day. As pointed, several findings were likely to be affected by the timing after symptom onset, such as absent of pulmonary lesion and SARS-CoV-2 viral load in the nasal-swab specimens, whereas the association between dominant CT pattern (extended GGO and segmental OP) did not merely affect by the timing (Table 3 in the paper). As we already mentioned as the limitation of this study, the variation of CT-evaluated timing may carry a bias. It would be ideal to further investigate the time-dependent change of CT pattern to clarify this effect, in relate with nasal-swab viral load and RNAemia. However, since the primary objectives of this study were to assess the association between the dominant CT pattern in the early phase of SARS-CoV-2 infection and the development of “hypoxemic respiratory failure” (not mortality), we believe that the timing of the CT did not have a major effect on the results, because all these CTs were taken before the initiation of any therapy, including oxygen administration.

Second, no significant association between D-dimer levels and respiratory failure was found in this study (shown at Table 1 in the paper). Despite of the significant association between extended ground-glass opacities pattern (ex GGO) and RNAemia, D-dimer levels did not differ between the dominant CT patterns. Because D-dimer reflect coagulation activation in critically severe COVID-19 [2-5], the relatively fewer patients with fatal/critical COVID-19 in this study (12% of the whole cohort) might have affected the diagnostic value of D-dimer. Based on these, we speculate that the CT pattern, in particular ex GGO, potentiate to sensitively reflect SARS-CoV-2 vessel invasion, even in the early phase or mild case in COVID-19.

We thank again Furkan Ufuk for his very pertinent analysis of our article that helped us to enhance its quality.