Immunology: Impaired antiviral responses in patients with severe COVID-19

Patients with severe COVID-19 have antibodies that inhibit an effective antiviral response, according to research published in Nature today. An analysis of 21 patients with mild or severe COVID-19 reveals that, in patients with severe disease, the immune system fails to generate the protective cell populations found in mild disease. Potential targets for treatments that could re-engage an antiviral response are identified in the paper.

Matthew Krummel and colleagues investigate the differences in immune responses between patients with mild or severe COVID-19 (11 and 10 patients, respectively). Patients with mild COVID-19 produce protective immune cells via a process called interferon-induced gene expression; interferons are signalling proteins released in response to infections, triggering immune cells to attack the virus while also having a direct inhibitory effect on viral entry into host cells. However, interferon-stimulated gene expression profiles were reduced in patients with severe disease, in all the immune populations analyzed in the study. The authors demonstrate that patients with severe COVID-19 produce antibodies that actively inhibit the production of the protective interferon-stimulated immune cells.

Experiments to identify the mechanism for inhibition of the immune response highlighted a signalling pathway that is responsible for the inhibition of interferon-stimulated gene expression program in patients with severe COVID-19. The authors suggest that drugs known to inhibit the specific signalling pathway, represent a potential novel line of immunotherapy treatment for patients with COVID-19, that could protect those patients from severe disease symptoms. Further work is needed to study antibody responses in COVID-19, and the authors conclude that it is likely that the exact nature of the antibody response may vary among patients.