SARS-CoV-2-Infection (COVID-19): Clinical Course, Viral Acute Respiratory Distress Syndrome (ARDS) and Cause(s) of Death

Abstract

SARS-CoV-2-infected symptomatic patients often suffer from high fever and loss of appetite which are responsible for the deficit of fluids and of protein intake. Many patients admitted to the emergency room are, therefore, hypovolemic and hypoproteinemic and often suffer from respiratory distress accompanied by ground glass opacities in the CT scan of the lungs. Ischemic damage in the lung capillaries is responsible for the microscopic hallmark, diffuse alveolar damage (DAD) characterized by hyaline membrane formation, fluid invasion of the alveoli, and progressive arrest of blood flow in the pulmonary vessels. The consequences are progressive congestion, increase in lung weight, and progressive hypoxia (progressive severity of ARDS). Sequestration of blood in the lungs worsens hypovolemia and ischemia in different organs. This is most probably responsible for the recruitment of inflammatory cells into the ischemic peripheral tissues, the release of acute-phase mediators, and for the persistence of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autopsy studies have been performed mostly in patients who died in the ICU after SARS-CoV-2 infection because of progressive acute respiratory distress syndrome (ARDS). In the death certification charts, after respiratory insufficiency, hypovolemic heart failure should be mentioned as the main cause of death.

Keywords: SARS-CoV-2 infection; acute respiratory distress syndrome; cause of death; dehydration; diffuse alveolar damage (DAD); heart failure; hyaline membrane; hypoalbuminemia; lung weight; pulmonary engorgement; pulmonary hypoxia.

Figure 1

Macroscopic picture of a lung taken during a post-mortem autopsy of a patient who was admitted at the Mount Sinai Hospital and died because of SARS-CoV-2 infection. The gross appearance resembles that of a solid organ with “patchy” areas of consolidation (A). The microscopic picture (B) shows the “congestion” of the alveolar capillaries, which may represent the initial episode of the lung changes accompanied by fibrin deposits (blue arrow) of the article published by Bryce C et al. in Modern Pathology 2021; 34:1456–1467 [40]).

Figure 2

Gross morphology (upper panel) from the lung of a patient who died after a SARS-CoV-1- infection shows a congested lung while the histology picture (lower panel) shows the hyaline membranes (blue arrows). Modified from Ding et al. [173].