Pulmonary Pathology of COVID-19 Following 8 Weeks to 4 Months of Severe Disease

A Report of Three Cases, Including One With Bilateral Lung Transplantation

Scott W. Aesif, MD, PhD; Alejandro C. Bribriesco, MD; Ruchi Yadav, MD; Summer L. Nugent, MD; Dmitriy Zubkus, MD; Carmela D. Tan, MD; Atul C. Mehta, MD; Sanjay Mukhopadhyay, MD

Disclosures

Am J Clin Pathol. 2021;155(4):506-514. 

In This Article

Abstract and Introduction

Abstract

Objectives: Current knowledge of the pulmonary pathology of coronavirus disease 2019 (COVID-19) is based largely on postmortem studies. In most, the interval between disease onset and death is relatively short (<1 month). Information regarding lung pathology in patients who survive for longer periods is scant. We describe the pathology in three patients with severe COVID-19 who underwent antemortem examination of lung tissue at least 8 weeks after initial diagnosis.

Methods: We conducted a retrospective case series.

Results: The first patient developed acute respiratory failure and was started on extracorporeal membrane oxygenation (ECMO) on day 21, with subsequent hemothorax. Debridement (day 38) showed extensive lung infarction with diffuse alveolar damage and Candida overgrowth. The second patient developed acute respiratory failure requiring mechanical ventilation that did not improve despite ECMO. Surgical lung biopsy on day 74 showed diffuse interstitial fibrosis with focal microscopic honeycomb change. The third patient also required ECMO and underwent bilateral lung transplantation on day 126. The explanted lungs showed diffuse interstitial fibrosis with focal microscopic honeycomb change.

Conclusions: This series provides histologic confirmation that complications of COVID-19 after 8 weeks to 4 months of severe disease include lung infarction and diffuse interstitial fibrosis.

Introduction

In a time without precedent to living memory, the ongoing and evolving coronavirus disease 2019 (COVID-19) pandemic has affected millions worldwide. Our current understanding of COVID-19 pathology is based almost entirely on autopsies (both complete and partial) and postmortem biopsies performed on patients dying after a few days to a few weeks of severe disease.[1–25] In one series, the interval between onset of illness and death ranged from 1 to 32 days.[25] In another, the range was 1 to 58 days (median, 21 days).[23] A series of 30 "minimally invasive autopsies" included six patients with duration of illness listed as 63, 68, 75, 63, 71, and 82 days.[6] Not unexpectedly, the most striking degree of tissue damage has consistently been reported in the lungs. Like most severe viral pneumonias, the pattern of injury most often encountered on histologic review is diffuse alveolar damage (DAD), which is the expected histologic correlate to the acute respiratory distress syndrome (ARDS).[26–28] These findings are similar to reports from previous coronavirus-related outbreaks (ie, severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]).[29–31] Fifteen percent to 30% of patients who recovered from SARS and MERS went on to develop persistent long-term lung abnormalities, including pulmonary fibrosis.[30–32] Similarly, the natural progression of infectious and noninfectious ARDS has long been thought to include the potential for long-term pulmonary complications, including the development of significant and irreversible pulmonary fibrosis.[26–28] Although this remains to be proven at a histologic level in COVID-19, if we extrapolate data from prior outbreaks of severe viral disease to the current pandemic, it seems plausible that long-term complications following recovery from COVID-19 infection will be encountered in coming months and years.

In addition to the lack of pathologic information regarding antemortem pulmonary changes associated with COVID-19, there is little information regarding pathologic findings in the lungs of patients who survived initial infection but remained severely ill for more than a few weeks. In the first such case reported, the explanted lungs of a 44-year-old woman who underwent bilateral lung transplantation on day 58 showed large zones of necrosis, DAD, and widespread thromboemboli.[33] Interestingly, while cultures were negative at the time of transplantation, polymerase chain reaction (PCR) testing remained positive. Two earlier preliminary reports from China documented the feasibility of lung transplantation for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-negative patients.[34,35] Of the five patients reported, histologic assessments were only reported for two patients, both as "extensive pulmonary interstitial fibrosis," with varying descriptions of thrombosis and hemorrhage. No other histologic data were provided, and the interval between disease onset and transplantation was not explicitly stated.

Here we report the antemortem pathologic findings in the lungs of three patients who survived with severe COVID-19 for intervals ranging from 8 weeks to 4 months (range, 57–126 days) followed by surgical lung biopsy/resection, autopsy, or lung transplantation.

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