Heightened immune responses found in patients with severe COVID-19 infection

Earlier studies on abnormal immune responses to coronavirus were restricted to animal models.

This is the first time the abnormal immune responses to coronavirus infection has been studied in patients with severe and moderate disease.

Studying the bronchoalveolar lavage fluid taken from six patients with severe COVID-19 infection and three with moderate disease, researchers characterised the underlying immune responses to novel coronavirus (SARS-CoV-2) in the two patient categories in comparison with controls (health individuals). The nine patients studied had a median age of 57 and included six men and three women.

The team of researchers led by Zheng Zhang from the National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, China published the results in Nature Medicine .

This is the first time the abnormal immune responses to coronavirus infection has been studied in patients with severe and moderate disease. Earlier studies on abnormal immune responses to coronavirus were restricted to animal models. The study shed light on how cytokine storm is associated with severe COVID-19. However, the study has a couple of limitations — small sample size of nine patients studied and lack of longitudinal samples collected before and after infection.

The bronchoalveolar lavage samples from patients who had severe COVID-19 had higher concentration of macrophages and neutrophils (types of white blood cell) than patients with moderate disease and healthy controls. Also, the patients with severe disease had higher concentration of inflammatory cytokines (particularly interleukin (IL)-8, IL-6 and IL-1β) compared with patients with moderate disease.

The higher concentration of macrophages, neutrophils and inflammatory cytokines revealed the inflammatory macrophage microenvironment present in the lungs of patients with severe disease. Lung macrophages in patients with severe disease may contribute to local inflammation by recruiting inflammatory monocytic cells and neutrophils, whereas macrophages in patients with moderate disease produce more T cell-attracting chemokines (signaling proteins released by immune cells).

“These findings suggest that a highly proinflammatory macrophage microenvironment is present in the lungs of patients with severe COVID-19, which is consistent with previous knowledge of macrophage populations during steady-state, inflammation and recovery,” they write.

In addition to studying macrophages and inflammatory cytokines, the researchers studied diverse T cells (another type of white blood cells). Compared with patients with moderate disease, they found patients with severe disease had higher levels of proliferating T cells but lower proportion of CD8+ T cells. The anti-viral immune responses of the CD8+ T cells play an important role in disease control by killing the infected cells.

Patients with moderate disease had a higher proportion of the much required CD8+ T cells and lower levels of proliferating T cells. “Our data suggest that CD8+ T cells in lavage samples from patients with severe/critical infection were less expanded, more proliferative and more phenotypically heterogeneous, whereas a larger proportion of CD8+ T cell effectors with tissue-resident and highly expanded features were present in lavage samples from patients with moderate infection,” they write.