The majority of patients with severe COVID-19 develop unusually pronounced scarring of the lungs, due to misguided immune response, according to a study.

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A team of researchers led by Charite - Universitatsmediz in Berlin, in the journal Cell, reported that macrophages -- immune cells which engulf and digest foreign substances -- play a central role. In patients with severe COVID-19, damage to the lungs is so severe that the body can no longer absorb sufficient oxygen from the air -- a condition is known as Acute Respiratory Distress Syndrome (ARDS).

"At the very least, SARS-CoV-2 is a potential trigger for a misguided macrophage response," explained Prof. Dr. Matthias Selbach, from the Max DelbrAck Center for Molecular Medicine (MDC). "Rather than replicating inside the immune cells, the virus appears to reprogramme them," he added.

The researchers considered a number of potential causes for this prolonged lung failure, including a particular type of ARDS, which causes pulmonary scarring leading to tissue thickening and stiffness. Tissue remodelling of this type (known as a fibrosis) had been observed in certain patients relatively early on in the pandemic.

As part of their research, the team used a number of microscopic imaging techniques to study lung tissue from deceased COVID-19 patients. "Almost all affected patients showed extensive tissue damage. The majority of the alveoli had been destroyed and the alveolar walls showed extensive thickening. We also found ubiquitous deposits of collagen, the main component of scar tissue. All of this is characteristic of severe fibrosis," said Prof. Dr. Peter Boor, lead at the RWTH Aachen University Medical Center's Institute of Pathology.

The reason for this phenomenon was initially unclear. In patients with COVID-19, respiratory failure typically only develops in week two or three after symptom onset, at a point when viral loads have started to decline. "This suggests that lung failure is not caused by the uncontrolled viral replication, but by secondary host responses, including those involving the immune system," explained Prof. Dr. Leif Erik Sander of Charite's Department of Infectious Diseases and Respiratory Medicine.

The researchers, therefore, analysed the composition and characteristics of immune cells taken from bronchioalveolar lavage and lung tissue samples of severe and deceased COVID patients. They found that the pronounced accumulation of macrophages is one of the key features in COVID-19 patients who develop respiratory failure. Using cell cultures, the researchers discovered that SARS-CoV-2 exerts an effect on macrophages which may, in turn, accelerate the process of fibrosis.