Pulmonary Parenchymal Changes in COVID-19 Survivors

Abstract

Background: As the COVID-19 pandemic moves into the survivorship phase, questions regarding long-term lung damage remain unanswered. Previous histopathologic studies are limited to autopsy reports. We studied lung specimens from COVID-19 survivors who underwent elective lung resections to determine whether postacute histopathologic changes are present.

Methods: This multicenter observational study included 11 adult COVID-19 survivors who had recovered but subsequently underwent unrelated elective lung resection for indeterminate lung nodules or lung cancer. We compared these against an age- and procedure-matched control group who never contracted COVID-19 (n = 5) and an end-stage COVID-19 group (n = 3). A blinded pulmonary pathologist examined the lung parenchyma focusing on 4 compartments: airways, alveoli, interstitium, and vasculature.

Results: Elective lung resection was performed in 11 COVID-19 survivors with asymptomatic (n = 4), moderate (n = 4), and severe (n = 3) COVID-19 infections at a median 68.5 days (range 24-142 days) after the COVID-19 diagnosis. The most common operation was lobectomy (75%). Histopathologic examination identified no differences between the lung parenchyma of COVID-19 survivors and controls across all compartments examined. Conversely, patients in the end-stage COVID-19 group showed fibrotic diffuse alveolar damage with intra-alveolar macrophages, organizing pneumonia, and focal interstitial emphysema.

Conclusions: In this study to examine the lung parenchyma of COVID-19 survivors, we did not find distinct postacute histopathologic changes to suggest permanent pulmonary damage. These results are reassuring for COVID-19 survivors who recover and become asymptomatic.

Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Representative computed tomographic (CT) images from a patient who recovered from severe COVID-19 infection and then subsequently underwent a right lower lobectomy. (A) Axial CT images 3 weeks after the COVID-19 diagnosis show bilateral patchy ground-glass opacities. (B) Axial CT from positron emission tomography/CT images 6 weeks later show resolution of the bilateral ground-glass opacities and the 2.45-cm lung nodule prompting the right lower lobectomy.

Figure 2

Amount of time from COVID-19 infection to operation. Time from positive COVID-19 reverse-transcription polymerase chain reaction (RT-PCR) test to elective thoracic operation date for COVID-19 survivors and patients with COVID-19 end-stage lung disease, with the exception of patient 19 who did not undergo an operation.

Figure 3

Representative histologic images (hematoxylin and eosin stain; original magnification ×20) of the airways. (A) COVID-19 survivor (patient 11) with basement membrane fibrosis (arrow) and scant submucosal inflammation. (B) Negative control (patient 5) shows similar basement membrane fibrosis (arrow). (C) COVID-19 end-stage lung disease (patient 19) exhibits postmortem sloughing and scant lymphocytic inflammation in the submucosa. (D) COVID-19 end-stage lung disease (patient 17) with basement membrane fibrosis (arrow) and moderate submucosal and intraepithelial inflammation. Scale bars (bottom left corner): ∼250 μm.

Figure 4

Representative histologic images (hematoxylin and eosin stain) of the alveoli and interstitial regions. (A) COVID-19 survivor (patient 10) with mild, variable interstitial thickening (original magnification ×20). (B) Negative control (patient 5) shows similar interstitial thickening (original magnification ×20). (C) COVID-19 end-stage lung disease (patient 19) exhibits diffuse alveolar damage (original magnification ×10). (D) COVID-19 end-stage lung disease (patient 17) with scattered intra-alveolar macrophages and fibrotic diffuse alveolar damage (original magnification ×10), with interstitial fibrosis supported by positive trichrome staining in the interstitium (inset original magnification ×10). Scale bars (bottom left corner): ∼250 μm.

Figure 5

Representative histologic images (hematoxylin and eosin stain) of pulmonary vasculature. (A) COVID-19 survivor (patient 10) with pulmonary hypertension (original magnification ×10). (B) Negative control (patient 4) with similar pulmonary hypertension as well as mild interstitial inflammation (original magnification ×10). (C) COVID-19 end-stage lung disease (patient 19) with minimal vascular changes (original magnification ×20). (D) COVID-19 end-stage lung disease (patient 17) shows a recanalized thrombus (original magnification ×20 magnification). Scale bars (bottom left corner): ∼250 μm.