Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of COVID-19 death

Abstract

Most COVID-19 victims are old and die from unrelated causes. Here we present t welve complete autopsies, including two rapid autopsies of young patients where the cause of death was COVID-19 ARDS. The main virus induced pathology was in the lung parenchyma and not in the airways. Most coagulation events occurred in the intra-alveolar and not in the intra-vascular space and the few thrombi were mainly composed of aggregated thrombocytes. The dominant inflammatory response was the massive accumulation of CD163+ macrophages and the disappearance of T killer, NK and B-cells. The virus was replicating in the pneumocytes and macrophages but not in bronchial epithelium, endothelium, pericytes or stromal cells. The lung consolidations were produced by a massive regenerative response, stromal and epithelial proliferation and neovascularization. We suggest that thrombocyte aggregation inhibition, angiogenesis inhibition and general proliferation inhibition may have a roll in the treatment of advanced COVID-19 ARDS.

A COVID-19-association-dependent categorization of death causes in 100 autopsy cases

“…Among biomarkers, abnormal values for CRP, D-Dimer (>80%), IL-6, ferritin, urea nitrogen, GGT, LDH, NT-proBN, and neutrophil count were detected in >60% of patients. This agrees with demonstrations of elevated values for CRP, D-Dimer, IL-6, and ferritin in COVID-19 patients [ 8 , 19 , 33 ]. Increased CRP values reportedly are characteristic in COVID-19 but not in other viral infections [ 34 ].…”

“…Among affected organs, pulmonary injury was the most severe among on both macroscopic and histologic examination, as reported in previous studies [ 4 , 5 , 8 – 10 , 14 , 15 , 19 , 22 , 35 ]. The most pronounced major histological findings were the bilateral, but non-uniformly distributed exudative, proliferative, and fibrotic stages of diffuse alveolar damage (DAD), with microthrombi and macrothrombi, also as noted by others [ 6 , 8 , 14 , 17 , 19 , 35 ]. Features included fibrin-rich alveolar fluid, multinucleated giant cells, and an abundance of alveolar macrophages previously described [ 19 ].…”

“…The most pronounced major histological findings were the bilateral, but non-uniformly distributed exudative, proliferative, and fibrotic stages of diffuse alveolar damage (DAD), with microthrombi and macrothrombi, also as noted by others [ 6 , 8 , 14 , 17 , 19 , 35 ]. Features included fibrin-rich alveolar fluid, multinucleated giant cells, and an abundance of alveolar macrophages previously described [ 19 ]. A general impression garnered was that changes otherwise separately present in lung disease, such as usual interstitial pneumonia, desquamative interstitial pneumonia, and organizing pneumonia, in Covid-pneumopathy were superimposed on one another.…”

“…A general impression garnered was that changes otherwise separately present in lung disease, such as usual interstitial pneumonia, desquamative interstitial pneumonia, and organizing pneumonia, in Covid-pneumopathy were superimposed on one another. According to Székely et al [ 19 ], most coagulation events were detected in the intraalveolar and not in the intra-vascular spaces. The histopathological picture of COVID-19 pulmonary findings was classified as epithelial, vascular, and fibrotic patterns of injury, reflecting the different stages in pathophysiological “timeline” of the disease.…”

“…SARS-CoV-2 nucleocapsid and spike proteins were detected immunohistochemically in pneumocytes and in detached cells in the alveolar lumen; coughed-up alveolar contents thus might transmit infective virus. Others also have immunohistochemically detected viral proteins in a similar distribution [ 6 , 18 ] as well as viral RNA using in situ hybridization [ 19 ]. Bronchial changes were mainly associated with intubation, with severe purulent bronchitis with bacterial colonies noted.…”