COVID-19 revisiting inflammatory pathways of arthritis

Abstract

Coronavirus disease 2019 (COVID-19) is an infectious disease, caused by severe acute respiratory syndrome coronavirus 2, which predominantly affects the lungs and, under certain circumstances, leads to an excessive or uncontrolled immune activation and cytokine response in alveolar structures. The pattern of pro-inflammatory cytokines induced in COVID-19 has similarities to those targeted in the treatment of rheumatoid arthritis. Several clinical studies are underway that test the effects of inhibiting IL-6, IL-1β or TNF or targeting cytokine signalling via Janus kinase inhibition in the treatment of COVID-19. Despite these similarities, COVID-19 and other zoonotic coronavirus-mediated diseases do not induce clinical arthritis, suggesting that a local inflammatory niche develops in alveolar structures and drives the disease process. COVID-19 constitutes a challenge for patients with inflammatory arthritis for several reasons, in particular, the safety of immune interventions during the pandemic. Preliminary data, however, do not suggest that patients with inflammatory arthritis are at increased risk of COVID-19.

Fig. 1. Range of arthritis symptoms associated with infections.

Musculoskeletal symptoms that can develop during viral infections, including coronavirus infections, range from arthralgia to chronic arthritis. ^aCoronaviruses refer to the zoonotic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 and Middle East respiratory syndrome CoV (MERS-CoV). ^bChikungunya, Ross River, Barmah Forest, Sindbis, O’nyong-nyong and Mayaro viruses.

Fig. 2. Alveolar inflammation in COVID-19.

a | In mild disease, the adaptive immune response leads to the clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the lung. b | In severe coronavirus disease 2019 (COVID-19), an excessive or uncontrolled innate immune response leads to a cytokine storm and acute respiratory distress syndrome (ARDS). AT1, alveolar type 1; AT2, alveolar type 2; BMM, bone-marrow-derived macrophage; GM-CSF, granulocyte–monocyte colony-stimulating factor; IFN, interferon; PAMPs, pathogen-associated molecular patterns; pDC, plasmacytoid dendritic cell; PMN, polymorphonuclear granulocyte.