In the early months of the outbreak (2020–2022), COVID-19 was responsible for acute respiratory distress syndrome (ARDS) and an exceptional number of intensive care unit (ICU) admissions. Weaning difficulties from invasive mechanical ventilation (IMV) and many deaths related to COVID-19 were associated with persistent pulmonary hyperinflammation leading to pulmonary fibrosis and sometimes, in the first wave of the pandemic and before the use of dexamethasone was introduced, pulmonary cystic necrosis. A 72-year-old man hospitalized with severe COVID-19 required IMV and died on day 31 of refractory ARDS. Postmortem examination of the lungs found obliterative endotheliitis proximal to pulmonary cystic necrosis. The presence of SARS-CoV-2 envelope and complement/lectin (MASP-2) deposits near the endotheliitis lesions suggested that the virus acted directly on vascular involvement by a complement-mediated mechanism. Together with classic features of ARDS (epithelial lesions and diffuse alveolar damage), endothelial involvement with endotheliitis was the hallmark of severe COVID-19. Corticosteroids and complement blockade were sometimes beneficial for treating severe COVID-19, perhaps by preventing microvascular damage.
