Autopsy findings after long-term treatment of COVID-19 patients with microbiological correlation

Abstract

Between April and June 2020, i.e., during the first wave of pandemic coronavirus disease 2019 (COVID-19), 55 patients underwent long-term treatment in the intensive care unit at the University Hospital of Regensburg. Most of them were transferred from smaller hospitals, often due to the need for an extracorporeal membrane oxygenation system. Autopsy was performed in 8/17 COVID-19-proven patients after long-term treatment (mean: 33.6 days). Autopsy revealed that the typical pathological changes occurring during the early stages of the disease (e.g., thrombosis, endothelitis, capillaritis) are less prevalent at this stage, while severe diffuse alveolar damage and especially coinfection with different fungal species were the most conspicuous finding. In addition, signs of macrophage activation syndrome was detected in 7 of 8 patients. Thus, fungal infections were a leading cause of death in our cohort of severely ill patients and may alter clinical management of patients, particularly in long-term periods of treatment.

Keywords: Autopsy; COVID-19; Fungal infection; Macrophage activation syndrome; Mycosis.

Fig. 1

Macroscopical lung pathology: White nodules with sharply demarcated borders (a P1, b P2, arrow). In c, a mixture of dark red and paler brown lung parenchyma is visible (P5). Thrombi within peripheral branches of the pulmonary artery (arrowhead d P7, e P4). d Additional icteric changes (P7). In e, the thrombus is accompanied by a hemorrhagic infarction of the lung (P4)

Fig. 2

Histological findings in COVID-19-deceased: Typical changes of the lung in COVID-19 deceased with hyperplasia of type II pneumocytes (a P5, arrowhead, HE, original magnification × 200), accompanying giant cells (b P5, arrowhead, HE, original magnification × 400), and squamous metaplasia (c P5, arrow, HE, original magnification × 200). Next to this, a small fresh hyaline microthrombus could be found (c: arrowhead). Sepsis-associated hepatic injury with marked cholestasis and steatosis (d P3, HE, original magnification × 100). Liver cirrhosis (e P4, HE, original magnification × 40) with globules of alpha-1-antitrypsin (f P4, Alpha-1-Antitrypsin, type PIZ, original magnification × 400). Bone marrow with signs of macrophage activation syndrome (g P1, arrowhead, PAS, original magnification × 400; h P1, arrow, CD68, original magnification × 400)

Fig. 3

Histological examples of diffuse alveolar damage (DAD) observed in this study: Very early stages of exudative damage (acute pattern) such as alveolar cell desquamation, congestion, and loss of type 1-pneumocytes were only rarely seen (a). Also, typical hyaline membranes (= alveolar fibrin deposits; arrows), which develop later during the acute (exudative) pattern (b), could only be demonstrated occasionally. In addition, most of these hyaline membranes already showed signs of beginning fibrosis (c; arrows on fibrin, asterisks on organizing foci), classifying these cases as being an intermediate step (= proliferative pattern) to the fibrotic stage. Corresponding to the generally long duration of mechanical ventilation (mean 29 days), DAD in our patients often corresponded to early fibrotic stages, characterized by myofibroblast proliferation with increasing interstitial as well as alveolar collagen deposition (d). Only one patient (patient 8) showed a severe pulmonary fibrosis with dense collagen deposits, large areas of nearly complete loss of normal alveolar architecture and elastic fibers and microcysts as a final and fatal consequence of DAD (e). Respiratory failure was also the main cause of death in this case. Original magnification: × 200 (a, b), × 400 (c), × 100 (d), × 40 (e). Staining: HE (a–d), elastic van Gieson (e)

Fig. 4

Fungal infection in different organs: Angionvasive aspergillosis of the lung (a P1, arrow, HE, original magnification × 100; b P1, Grocott, original magnification × 200). Zygomycetes species in the wall of the large bowel (c P3, arrow, PAS, original magnification × 400; d P3, Grocott, original magnification × 400). Acute inflammation of the lung with zygomycetes species (e P4, HE, original magnification × 200; f P4, arrow, HE, original magnification × 400). Aspergillus species within the wall of an esophageal ulcer (g P5, HE, original magnification × 200; h P5, arrow, PAS, original magnification × 200)