The pulmonary pathobiology of patients who died from respiratory failure caused by coronavirus disease 2019 (COVID-19) vs influenza was found to be distinct, according to a study published in the New England Journal of Medicine.
A total of 24 lungs were obtained during the autopsy of patients who died from COVID-19 (n=7), from acute respiratory distress syndrome (ARDS) caused by influenza A (H1N1; n=7), or from causes other than infection (n=10). The lungs from patients infected with H1N1 were collected in 2009 and the lungs from control individuals were matched for age. Lungs were examined using a 7-color immunohistochemical analysis, micro-computed tomographic imaging, scanning electron microscopy, corrosion casting, and gene expression analysis through direct multiplexed measurement.
The lungs from patients who died from COVID-19 were from 2 women (mean age, 68±9.2 years) and 5 men (mean age, 80±11.5 years). The H1N1 lungs were from 2 women (mean age, 62.5±4.9 years) and 5 men (mean age, 55.4±10.9 years). The control lungs were from 5 women (mean age, 68.2±6.9 years) and 5 men (mean age, 79.2±3.3 years).
The lungs from patients with COVID-19 vs H1N1 were (2404±560 g vs 1681±49 g, respectively; P =.04), and lungs from control individuals (1045±91 g) were lighter compared with those from patients with COVID-19 and H1N1 vs (P <.001 and P =.003, respectively).
Lungs from individuals who died from COVID-19 and H1N1 exhibited diffuse alveolar damage with perivascular T-cell infiltration which were not observed in lungs from healthy controls. COVID-19 lungs also had distinctive vascular features of severe endothelial injury caused by the presence of the virus which disrupted cell membranes. This endothelial injury was not observed in control or H1N1 lungs.
The histologic analysis revealed widespread thrombosis with microangiopathy in COVID-19 and H1N1 lungs, and the lungs from patients with COVID-19 had 9 times the amount of alveolar capillary microthrombi when compared with lungs from patients with H1N1 (P <.001). New vessel growth due to intussusceptive angiogenesis was 2.7 times greater in COVID-19 lungs compared with H1N1 lungs (P <.001).
The number of CD4-positive T-cells were higher for COVID-19 lungs than for H1N1 (13.6±6.0 vs 5.8±2.5, respectively; P =.04) and the number of CD8-positive T-cells was reduced in COVID-19 vs H1N1 tissue (5.3±4.3 vs 11.6±4.9 respectively; P =.008) as were CD15-positive neutrophils (0.4±0.5 vs 4.8±5.2 respectively; P =.002). Lungs of patients with COVID-19 and H1N1 had altered expression for 69 and 26 angiogenesis-related genes, respectively. .
Study limitations include the small number of lungs and the fact that autopsy does not inform on disease evolution. The possible role of mechanical ventilation on disease progression and death remains unclear. None of the patients with COVID-19 received mechanical ventilation, but 5 of the 7 patients with H1N1 did. Due to this imbalance, the investigators were unable to address questions about the impact of ventilation.
“Our finding of enhanced intussusceptive angiogenesis in the lungs from patients with COVID-19 as compared with the lungs from patients with influenza was unexpected,” noted the research authors. “New vessel growth can occur by conventional sprouting or intussusceptive (nonsprouting) angiogenesis. The characteristic feature of intussusceptive angiogenesis is the presence of a pillar or post spanning the lumen of the vessel.”
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Ackermann M, Verleden S E, Kuehnel M, et al. Pulmonary vascular endothelialitis thrombosis, and angiogenesis in COVID-19. N Engl J Med. 2020;383(2):120-128.
This article originally appeared on The Cardiology Advisor