Long COVID in Immunocompromised and Immunocompetent Patients: A Clinical, Morphologic, and Virologic Portrait.

Context.—: Coronavirus disease 2019 (COVID) primarily affects the lung and can lead to chronic/post-COVID syndrome. Some insights about late pulmonary changes occurring in patients recovering from COVID have been published, but the evidence of detailed pathologic changes coming from follow-up care patients with long COVID is limited.

Objective.—: To evaluate tissue morphologic and viral features in transbronchial biopsies of long COVID patients (immunocompetent and immunocompromised).

Design.—: This retrospective observational study included 18 patients (9 immunocompetent and 9 immunocompromised) who were consecutively referred to outpatient clinic for post-COVID pneumonia, undergoing transbronchial biopsy. Several histologic changes were analyzed by computer-assisted morphometric analysis. As organizing pneumonia (OP) was consistently detected, fibrosis and inflammation were also evaluated in transbronchial biopsies from 28 control patients with histologic confirmation of OP. Tissue SARS-CoV-2 and the subgenomic transcripts were investigated. Morphologic findings were correlated with clinical and radiologic data.

Results.—: Long COVID patients showed lower inflammation than controls (P < .001) despite a similar fibrotic extension. When considering separately the 2 long COVID groups, the same inflammatory infiltrate extension was found, whereas a higher fibrotic remodeling characterized the immunocompetent subgroup (P = .05). Molecular investigation showed that SARS-CoV-2 was present in tissue samples obtained from 3 long COVID patients.

Conclusions.—: Long COVID patients showed a peculiar OP pattern, with more vascular and fibrotic changes. SARS-CoV-2 RNA, even in replicative status, can be detected in lung biopsies of both immunocompetent and immunocompromised patients. This pilot study is a forerunner of more in-depth lung tissue investigations to gain a better understanding of long COVID pathobiology.